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Zhang, Yuqi, and Michel F. Sanner. "AutoDock CrankPep: combining folding and docking to predict protein–peptide complexes." Bioinformatics 35, no. 24 (June 4, 2019): 5121–27. http://dx.doi.org/10.1093/bioinformatics/btz459.
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Abstract Motivation Protein–peptide interactions mediate a wide variety of cellular and biological functions. Methods for predicting these interactions have garnered a lot of interest over the past few years, as witnessed by the rapidly growing number of peptide-based therapeutic molecules currently in clinical trials. The size and flexibility of peptides has shown to be challenging for existing automated docking software programs. Results Here we present AutoDock CrankPep or ADCP in short, a novel approach to dock flexible peptides into rigid receptors. ADCP folds a peptide in the potential field created by the protein to predict the protein–peptide complex. We show that it outperforms leading peptide docking methods on two protein–peptide datasets commonly used for benchmarking docking methods: LEADS-PEP and peptiDB, comprised of peptides with up to 15 amino acids in length. Beyond these datasets, ADCP reliably docked a set of protein–peptide complexes containing peptides ranging in lengths from 16 to 20 amino acids. The robust performance of ADCP on these longer peptides enables accurate modeling of peptide-mediated protein–protein interactions and interactions with disordered proteins. Availability and implementation ADCP is distributed under the LGPL 2.0 open source license and is available at http://adcp.scripps.edu. The source code is available at https://github.com/ccsb-scripps/ADCP. Supplementary information Supplementary data are available at Bioinformatics online.
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Blaszczyk, Maciej, Maciej Pawel Ciemny, Andrzej Kolinski, Mateusz Kurcinski, and Sebastian Kmiecik. "Protein–peptide docking using CABS-dock and contact information." Briefings in Bioinformatics 20, no. 6 (September 20, 2018): 2299–305. http://dx.doi.org/10.1093/bib/bby080.
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Abstract CABS-dock is a computational method for protein–peptide molecular docking that does not require predefinition of the binding site. The peptide is treated as fully flexible, while the protein backbone undergoes small fluctuations and, optionally, large-scale rearrangements. Here, we present a specific CABS-dock protocol that enhances the docking procedure using fragmentary information about protein–peptide contacts. The contact information is used to narrow down the search for the binding peptide pose to the proximity of the binding site. We used information on a single-chosen and randomly chosen native protein–peptide contact to validate the protocol on the peptiDB benchmark. The contact information significantly improved CABS-dock performance. The protocol has been made available as a new feature of the CABS-dock web server (at http://biocomp.chem.uw.edu.pl/CABSdock/). Short abstract CABS-dock is a tool for flexible docking of peptides to proteins. In this article, we present a protocol for CABS-dock docking driven by information about protein–peptide contact(s). Using information on individual protein–peptide contacts allows to improve the accuracy of CABS-dock docking.
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Chan, Kiat Hwa, Jaehong Lim, Joo Eun Jee, Jia Hui Aw, and Su Seong Lee. "Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy." International Journal of Molecular Sciences 21, no. 24 (December 18, 2020): 9671. http://dx.doi.org/10.3390/ijms21249671.
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Diabetes-related neuropathy is a debilitating condition that may be averted if it can be detected early. One possible way this can be achieved at low cost is to utilise peptides to detect C-peptide, a biomarker of diabetic neuropathy. This depends on peptide-peptide co-assembly, which is currently in a nascent stage of intense study. Instead, we propose a bead-based triple-overlay combinatorial strategy that can preserve inter-residue information during the screening process for a suitable complementary peptide to co-assemble with C-peptide. The screening process commenced with a pentapeptide general library, which revealed histidine to be an essential residue. Further screening with seven tetrapeptide focused libraries led to a table of self-consistent peptide sequences that included tryptophan and lysine at high frequencies. Three complementary nonapeptides (9mer com-peptides), wpkkhfwgq (Trp-D), kwkkhfwgq (Lys-D), and KWKKHFWGQ (Lys-L) (as a negative control) were picked from this table for co-assembly studies with C-peptide. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) and circular dichroism (CD) spectroscopies were utilized to study inter-peptide interactions and changes in secondary structures respectively. ATR-FTIR studies showed that there is indeed inter-peptide interaction between C-peptide and the tryptophan residues of the 9mer com-peptides. CD studies of unaggregated and colloidal C-peptide with the 9mer com-peptides suggest that the extent of co-assembly of C-peptide with Trp-D is greatest, followed by Lys-D and Lys-L. These results are promising and indicate that the presented strategy is viable for designing and evaluating longer complementary peptides, as well as complementary peptides for co-assembly with other polypeptides of interest and importance. We discuss the possibility of designing complementary peptides to inhibit toxic amyloidosis with this approach.
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Raymond, Danielle M., and Bradley L. Nilsson. "Multicomponent peptide assemblies." Chemical Society Reviews 47, no. 10 (2018): 3659–720. http://dx.doi.org/10.1039/c8cs00115d.
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This review presents recent efforts in the development of multicomponent supramolecular peptide assemblies with a focus on multicomponent assemblies derived from β-sheet peptides, low molecular weight peptides, peptide amphiphiles, coiled coil peptides, collagen, and related systems.
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Anusha, G., and M. Monisha. "Molecular modeling and screening of antiviral peptides for Influenza A virus Polymerase basic protein 2(PB2) protein using Hpepdock software for the therapy of Influenza A." CARDIOMETRY, no. 25 (February 14, 2023): 1693–701. http://dx.doi.org/10.18137/cardiometry.2022.25.16931701.
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Aim: To determine the binding affinity (kcal/mol) for various antiviral peptides to target Influenza A virus PB2 protein using Hpepdock software and comparison with the Macrocyclic iHA100 peptide (Reference peptide). Materials and methods: The three-dimensional (3D) coordinates for PB2 protein were retrieved from Protein Data Bank (PDB ID 4P1U). The structures of 16 antiviral peptides were modeled using HPEPDOCK. The Molecular docking analysis of PB2 protein with derived antiviral peptides was performed using Hpepdock software. This software employs an algorithm that generates the output complexes based on the peptide conformations and orientations. Results: Molecular docking analysis revealed that antiviral peptides, P9R Peptide 2, P9R Peptide 3 and P9R Peptide 1, could bind PB2 protein with higher affinity in comparison with the reference Macrocyclic iHA-100 peptide. The antiviral peptides of P9R Peptide 2, P9R Peptide 3 and P9R Peptide 1 with p=0.786, p>0.05 insignificant (-202.728Kcal/mol), p=0.001, p<0.05 significant (-198.255 Kcal/mol), p=0.259, p>0.05 insignificant (-195,788 Kcal/mol) showed better results in comparison to reference Macrocyclic iHA-100 peptide (-154.392 Kcal/ mol). Conclusion: The identified antiviral peptides could more effectively inhibit PB2 protein than the other available peptides on the market to treat Influenza A viral disease.
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JACKSON, I. M. D. "Peptide Biology: Regulatory Peptides." Science 246, no. 4928 (October 20, 1989): 389–90. http://dx.doi.org/10.1126/science.246.4928.389-a.
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Erak, Miloš, Kathrin Bellmann-Sickert, Sylvia Els-Heindl, and Annette G. Beck-Sickinger. "Peptide chemistry toolbox – Transforming natural peptides into peptide therapeutics." Bioorganic & Medicinal Chemistry 26, no. 10 (June 2018): 2759–65. http://dx.doi.org/10.1016/j.bmc.2018.01.012.
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Ojcius, D. M., J. P. Abastado, A. Casrouge, E. Mottez, L. Cabanie, and P. Kourilsky. "Dissociation of the peptide-MHC class I complex limits the binding rate of exogenous peptide." Journal of Immunology 151, no. 11 (December 1, 1993): 6020–26. http://dx.doi.org/10.4049/jimmunol.151.11.6020.
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Abstract Soluble, single-chain molecules for two MHC class I alleles, H-2Kd and H-2Kb, were used to analyze the kinetics of antigenic peptide binding to MHC. After MHC preloading with radiolabeled or fluorescent peptides, the observed rate of MHC-peptide complex dissociation increased after addition of an excess of unlabeled competitor peptide. Although exogenous peptides conforming to the allele-specific motif were required for the enhanced complex dissociation to occur, the dissociation rate of the complex was independent of exogenous peptide concentration. Similarly, the association rate of exogenous peptides was independent of concentration, reflecting the presence of low affinity peptides in the binding sites of the recombinant MHC proteins; the sequences of these endogenous peptides conform to the consensus motif for the MHC allele studied. Finally, the association rate of exogenous peptide decreased when MHC molecules were preloaded with high affinity peptides, and the binding of labeled high affinity peptide to isolated recombinant MHC was faster than the subsequent dissociation observed in the presence of competitor peptide. Taken together, these results imply that the rate of exogenous peptide binding is limited by the dissociation rate of the previously bound peptides.
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El-Sayed Amr, Abd El-Galil, Mohamed Abo-Ghalia, and Mohamed M. Abdalah. "Synthesis of Novel Macrocyclic Peptido-calix[4]arenes and Peptidopyridines as Precursors for Potential Molecular Metallacages, Chemosensors and Biologically Active Candidates." Zeitschrift für Naturforschung B 61, no. 11 (November 1, 2006): 1335–45. http://dx.doi.org/10.1515/znb-2006-1104.
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Novel macrocyclic dipicolinic acid acylated peptides based on upper rim bridged peptidocalix[ 4]arenes, peptido-pyridines or hybrid structures of both, were synthesized as potential molecular metallacages and chemosensors. While conventional azide or mixed anhydride (ethyl chloroformate) peptide couplings served well for assembling the L-tyrosine or L-ornithine peptide backbones, the acid chloride of pyridine-2,6-dicarboxylic acid (dipicolinic acid) acid served as the complementary acylating agent. The structure assignment of the new compounds was based on chemical and spectroscopic evidences. Some of these compounds exhibit antimicrobial activities.
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Negroni, Maria, and Lawrence Stern. "Unexpected side reaction of lysine and arginine side chains preceding a photocleavable group in MHC-II UV-cleavable peptides. (P5028)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 41.15. http://dx.doi.org/10.4049/jimmunol.190.supp.41.15.
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Abstract MHC class II molecules (MHCII) present peptides to CD4+ T cells, and HLA-DM (DM) catalyzes peptide exchange favoring binding of high affinity peptides. The effects of DM on peptide association and dissociation kinetics are not yet clear. In the absence of peptide, DR1 (a MHCII) is in equilibrium between inactive and active conformations. In order to understand the kinetics of this process and how it is affected by DM, we wanted to generate DR1 in the active conformation using a peptide carrying the photocleavable 3-amino-3-(2-nitrophenyl)-propionic acid residue, an approach previously used for other MHCI and MHCII-binding peptides. We used well-characterized variants of a peptide derived from influenza hemagglutinin (HA). The variants bind to DR1 with an affinity similar to the parent HA peptide. Surprisingly, photolysis of peptides did not result in peptide release. Mass spectrometry showed that the main photoproduct had a mass decrease of 2Da, resulting from photocleavage followed by unexpected religation to a rearranged peptide that can still bind DR1. Replacement of peptide lysine (or arginine) residues by methionine yielded the expected cleavage products. The methionine substituted peptides can be used for further studies on DR1-peptide binding kinetics and the effect of DM on the different rates of the reaction. These studies provide a caveat to routine use of photocleavable peptides in MHC-peptide exchange studies.
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Servatius, Phil, Lukas Junk, and Uli Kazmaier. "Peptide Modifications: Versatile Tools in Peptide and Natural Product Syntheses." Synlett 30, no. 11 (April 2, 2019): 1289–302. http://dx.doi.org/10.1055/s-0037-1612417.
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Peptide modifications via C–C bond formation have emerged as valuable tools for the preparation and alteration of non-proteinogenic amino acids and the corresponding peptides. Modification of glycine subunits in peptides allows for the incorporation of unusual side chains, often in a highly stereoselective manner, orchestrated by the chiral peptide backbone. Moreover, modifications of peptides are not limited to the peptidic backbone. Many side-chain modifications, not only by variation of existing functional groups, but also by C–H functionalization, have been developed over the past decade. This account highlights the synthetic contributions made by our group and others to the field of peptide modifications and their application in natural product syntheses.1 Introduction2 Peptide Backbone Modifications via Peptide Enolates2.1 Chelate Enolate Claisen Rearrangements2.2 Allylic Alkylations2.3 Miscellaneous Modifications3 Side-Chain Modifications3.1 C–H Activation3.1.1 Functionalization via Csp3–H Bond Activation3.2.2 Functionalization via Csp2–H Bond Activation3.2 On Peptide Tryptophan Syntheses4 Conclusion
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Wang, P., G. Gyllner, and S. Kvist. "Selection and binding of peptides to human transporters associated with antigen processing and rat cim-a and -b." Journal of Immunology 157, no. 1 (July 1, 1996): 213–20. http://dx.doi.org/10.4049/jimmunol.157.1.213.
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Abstract Cytotoxic T lymphocytes recognize antigenic peptides presented by MHC class I molecules. The peptides are generated in the cytosol by proteasomes, and probably also other proteases, and are then translocated into the endoplasmic reticulum (ER) lumen. The transporters associated with Ag processing (TAP) are key molecules for transporting peptides from the cytosol to the lumen of the ER. Using semipermeabilized cells, TAP-dependent peptide translocation was demonstrated, and the selectivity of peptide translocation was based on the carboxyl-terminal amino acid of peptides. We have examined peptide binding proteins in the ER membrane and the selection of peptides for binding to TAP by using a panel of peptides of different sequences and carboxyl-termini as well as peptides containing D amino acids. Peptides bound to TAP molecules in the absence of ATP. The presence of ATP induced binding of peptides to two additional membrane proteins (58 and 43 kDa). The selection of peptides by TAP molecules was based on peptide sequence and the carboxyl-terminal amino acid. Peptides containing D amino acid did not bind to TAP molecules. Rat cim-a and -b selected peptides differently, and selection was not only dependent on the carboxyl-terminal residue of the peptide, but included an influence of the peptide sequence. The different off-rates after peptide binding to TAP, indicated a dual binding step of peptide to TAP. ATP regulated the off-rate of peptides at a high affinity binding step. Our results demonstrate that the binding of peptides to TAP molecules is specific and most likely involves a multiple step pathway.
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Negroni, Maria Pia, and Lawrence J. Stern. "The length of the N-terminal region of a photocleavable peptide bound to DR1 determines the kinetics of photocleavable peptide fragment release." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 185.1. http://dx.doi.org/10.4049/jimmunol.196.supp.185.1.
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Abstract MHC class II molecules (MHCII) bind peptides and present them to CD4+ T cells. As prepared as a recombinant protein, DR1 (a MHCII) is in equilibrium between peptide-receptive and peptide-averse conformations. In order to dissect which step of the peptide binding reaction is being affected in DR1 mutants with altered peptide affinity, we wanted to generate DR1 fully in the peptide-receptive conformation. To generate this form, we used a peptide carrying the photocleavable 3-amino-3-(2-nitrophenyl)-propionic acid residue, an approach previously used for other MHCI and MHCII proteins. We used variants of a well-characterized peptide derived from influenza hemagglutinin (HA), with different truncations at the N-terminal end, expecting to generate peptides with different affinity for DR1. This was confirmed by higher IC50 values obtained for the shorter peptides compared to the longer ones. All of the studied peptides were cleaved as expected after UV treatment as shown by mass spectrometry. However, when DR1-photocleavable peptide complexes were exposed to UV light, they generated different amounts of peptide-receptive DR1 measured by their ability to bind fluorescently-labeled HA peptide. The shorter the peptide, the more peptide-receptive DR1 was generated. This suggests that minimizing the interaction between photocleavable peptide and DR1 allows faster dissociation of the photo-generated fragments, and thus faster association of an incoming peptide. These results showed that the kinetics of photocleavable peptide fragment release can interfere with the kinetics of subsequent reactions.
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Shy, Adrianna N., Huaimin Wang, Zhaoqianqi Feng, and Bing Xu. "Heterotypic Supramolecular Hydrogels Formed by Noncovalent Interactions in Inflammasomes." Molecules 26, no. 1 (December 26, 2020): 77. http://dx.doi.org/10.3390/molecules26010077.
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The advance of structural biology has revealed numerous noncovalent interactions between peptide sequences in protein structures, but such information is less explored for developing peptide materials. Here we report the formation of heterotypic peptide hydrogels by the two binding motifs revealed by the structures of an inflammasome. Specifically, conjugating a self-assembling motif to the positively or negatively charged peptide sequence from the ASCPYD filaments of inflammasome produces the solutions of the peptides. The addition of the peptides of the oppositely charged and complementary peptides to the corresponding peptide solution produces the heterotypic hydrogels. Rheology measurement shows that ratios of the complementary peptides affect the viscoelasticity of the resulted hydrogel. Circular dichroism indicates that the addition of the complementary peptides results in electrostatic interactions that modulate self-assembly. Transmission electron microscopy reveals that the ratio of the complementary peptides controls the morphology of the heterotypic peptide assemblies. This work illustrates a rational, biomimetic approach that uses the structural information from the protein data base (PDB) for developing heterotypic peptide materials via self-assembly.
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Hörig, Heidi, Aideen C. M. Young, Nicholas J. Papadopoulos, Teresa P. DiLorenzo, and Stanley G. Nathenson. "Binding of Longer Peptides to the H-2Kb Heterodimer Is Restricted to Peptides Extended at Their C Terminus: Refinement of the Inherent MHC Class I Peptide Binding Criteria." Journal of Immunology 163, no. 8 (October 15, 1999): 4434–41. http://dx.doi.org/10.4049/jimmunol.163.8.4434.
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Abstract MHC class I molecules usually bind short peptides of 8–10 amino acids, and binding is dependent on allele-specific anchor residues. However, in a number of cellular systems, class I molecules have been found containing peptides longer than the canonical size. To understand the structural requirements for MHC binding of longer peptides, we used an in vitro class I MHC folding assay to examine peptide variants of the antigenic VSV 8 mer core peptide containing length extensions at either their N or C terminus. This approach allowed us to determine the ability of each peptide to productively form Kb/β2-microglobulin/peptide complexes. We found that H-2Kb molecules can accommodate extended peptides, but only if the extension occurs at the C-terminal peptide end, and that hydrophobic flanking regions are preferred. Peptides extended at their N terminus did not promote productive formation of the trimolecular complex. A structural basis for such findings comes from molecular modeling of a H-2Kb/12 mer complex and comparative analysis of MHC class I structures. These analyses revealed that structural constraints in the A pocket of the class I peptide binding groove hinder the binding of N-terminal-extended peptides, whereas structural features at the C-terminal peptide residue pocket allow C-terminal peptide extensions to reach out of the cleft. These findings broaden our understanding of the inherent peptide binding and epitope selection criteria of the MHC class I molecule. Core peptides extended at their N terminus cannot bind, but peptide extensions at the C terminus are tolerated.
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Yang, Yanlian, and Chen Wang. "Single-molecule studies on individual peptides and peptide assemblies on surfaces." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 371, no. 2000 (October 13, 2013): 20120311. http://dx.doi.org/10.1098/rsta.2012.0311.
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This review is intended to reflect the recent progress in single-molecule studies of individual peptides and peptide assemblies on surfaces. The structures and the mechanism of peptide assembly are discussed in detail. The contents include the following topics: structural analysis of single peptide molecules, adsorption and assembly of peptides on surfaces, folding structures of the amyloid peptides, interaction between amyloid peptides and dye or drug molecules, and modulation of peptide assemblies by small molecules. The explorations of peptide adsorption and assembly will benefit the understanding of the mechanisms for protein–protein interactions, protein–drug interactions and the pathogenesis of amyloidoses. The investigations on peptide assembly and its modulations could also provide a potential approach towards the treatment of the amyloidoses.
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Preet, Payal. "PEPTIDES: A NEW THERAPEUTIC APPROACH." International Journal of Current Pharmaceutical Research 10, no. 2 (March 15, 2018): 29. http://dx.doi.org/10.22159/ijcpr.2018v10i2.25887.
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Peptide therapeutics have played a notable role in medical practice since the advent of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States and other major markets, and peptides continue to enter clinical development at a steady pace. Peptide drug discovery has diversified beyond its traditional focus on endogenous human peptides to include a broader range of structures identified from other natural sources or through medicinal chemistry efforts. Peptides are recognized for being highly selective and efficacious and, at the same time, relatively safe and well tolerated. Consequently, there is an increased interest in peptides in pharmaceutical research and development (R and D), and approximately 140 peptide therapeutics are currently being evaluated in clinical trials. Given that the low-hanging fruits in the form of obvious peptide targets have already been picked, it has now become necessary to explore new routes beyond traditional peptide design. Examples of such approaches are multifunctional and cell-penetrating peptides, as well as peptide drug conjugates. In regards to patient compliance for drug delivery, oral drug delivery is generally the preferred route of administration. However, parental injection of peptide drugs has always been the primary method of peptide drug administration. Nevertheless, oral delivery of peptide drug presents a significant challenge due to the enzymatic degradation by enzymes in the GI tract and the poor penetration of the peptides across gastro-intestinal epithelium membranes, particularly for adults. Therefore, a novel peptide drug analogue or pro-drug that both protect peptide drugs from degradation by the enzymes in the GI tract that also improves its penetration across the intestinal epithelium membrane would greatly advance the development of peptide drugs as effective candidates for the treatment of various diseases.
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Tikhonov, S. L., N. V. Tikhonova, and E. A. Ulitina. "COMPARATIVE EVALUATION OF THE BIOLOGICAL EFFECT OF NATIVE AND SYNTHESIZED PEPTIDES." Vestnik of Immanuel Kant Baltic Federal University Series Natural and Medical Sciences, no. 3 (2023): 106–17. http://dx.doi.org/10.5922/gikbfu-2023-3-8.
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Biologically active peptides are considered as preventive and therapeutic agents for various diseases. Due to the high cost and complexity of isolating native peptides for use in pharmaceuticals, synthetically produced peptides are increasingly being used in dietary supplements. The aim of the research is to confirm the similarity and biological activity of synthesized peptides compared to native peptides. Synthesized and native peptides from bovine colostrum with the code names T1.1 and mpT2 were used as the objects of the study. The peptides were synthesized using the solid-phase method. Peptide T1.1 is similar to the peptide «POSSUM_01-POSSUM-C-EMBRYO-2KB», the biological activity of which has not been studied. Peptide mpT2 is similar to the anti-diabetic peptide «LL-16 Alytes obstetricans». It has been proven that the synthesized peptides do not differ from natural ones in terms of physical and chemical characteristics. Both synthesized and natural peptides are non-toxic. The anti-diabetic effect of natural and synthesized peptide mpT2 on animals with induced type 2 diabetes and the antioxidant activity of synthesized and natural peptide T1.1 have been demonstrated.
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Hendrikse, Erica R., Rebekah L. Bower, Debbie L. Hay, and Christopher S. Walker. "Molecular studies of CGRP and the CGRP family of peptides in the central nervous system." Cephalalgia 39, no. 3 (March 22, 2018): 403–19. http://dx.doi.org/10.1177/0333102418765787.
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Background Calcitonin gene-related peptide is an important target for migraine and other painful neurovascular conditions. Understanding the normal biological functions of calcitonin gene-related peptide is critical to understand the mechanisms of calcitonin gene-related peptide-blocking therapies as well as engineering improvements to these medications. Calcitonin gene-related peptide is closely related to other peptides in the calcitonin gene-related peptide family of peptides, including amylin. Relatedness in peptide sequence and in receptor biology makes it difficult to tease apart the contributions that each peptide and receptor makes to physiological processes and to disorders. Summary The focus of this review is the expression of calcitonin gene-related peptide, related peptides and their receptors in the central nervous system. Calcitonin gene-related peptide is expressed throughout the nervous system, whereas amylin and adrenomedullin have only limited expression at discrete sites in the brain. The components of two receptors that respond to calcitonin gene-related peptide, the calcitonin gene-related peptide receptor (calcitonin receptor-like receptor with receptor activity-modifying protein 1) and the AMY1 receptor (calcitonin receptor with receptor activity-modifying protein 1), are expressed throughout the nervous system. Understanding expression of the peptides and their receptors lays the foundation for more deeply understanding their physiology, pathophysiology and therapeutic use.
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de Kroon, A. I., and H. M. McConnell. "Kinetics and specificity of peptide-MHC class II complex displacement reactions." Journal of Immunology 152, no. 2 (January 15, 1994): 609–19. http://dx.doi.org/10.4049/jimmunol.152.2.609.
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Abstract The peptide-induced acceleration of the dissociation of pre-formed complexes of the detergent-solubilized mouse class II molecules IEd and IEk with fluorescein-labeled peptides was investigated using high-performance size exclusion chromatography. While it is generally believed that functional complexes of MHC class II alpha beta heterodimers and peptides have a 1:1 stoichiometry, the data provide qualitative as well as quantitative kinetic evidence that the enhancement of the release of one peptide by a second peptide is due to a two-peptide intermediate. Different combinations of peptides were tested for their ability to accelerate each other's release from IEd. The importance of positive charge for the interaction with IEd was confirmed by the finding that not only dynorphin 1-13 but also poly-L-lysine (14-19 mer) and a peptide corresponding to a mitochondrial presequence (net charge +6) efficiently enhance the release of pre-bound peptides. SDS-PAGE analysis revealed that the efficiently displacing peptides do not stabilize the IEd alpha beta heterodimer at acidic pH, in contrast to the IEd-restricted antigenic peptide HEL 107-116. The data support a mechanism in which the second peptide binds specifically to the pre-formed class II-peptide complex, which, depending on the properties of the peptides involved, leads to the destabilization of the complex and the release of the first peptide.
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Anusha, G., and M. Monisha. "Molecular Modeling and Screening of Antiviral peptides for HIV-Glycoprotein (gp41) using Hpepdock software for the therapy of AIDS (Acquired ImmunoDeficiency Syndrome)." CARDIOMETRY, no. 25 (February 14, 2023): 1702–10. http://dx.doi.org/10.18137/cardiometry.2022.25.17021710.
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Aim: To determine the binding affinity (Kcal/mol) for various antiviral peptides to target AIDS (Acquired Immunodeficiency Syndrome) gp41 protein. Materials and methods: The three-dimensional coordinates of gp41 protein were retrieved from Protein data bank(PDB ID 3VIE). The structures of 16 antiviral peptides were modeled using Hpepdock software. The Hpepdock software was used to perform a molecular docking investigation of gp41 with antiviral peptides. This software uses an algorithm to produce output complexes based on peptide conformations and orientations.The power calculation was done by clinical.cal.com, comparing binding affinity (kal/mol) for HIV virus gp41 protein Alpha error-threshold 0.05 power is 80% and for enrollment ratio-1. Results: Molecular docking analysis revealed that antiviral peptides namely, P9R peptide 3, M1 peptide 1 and P9 peptide 3 could bind gp41 protein with higher affinity in comparison with the reference Macrocyclic iHA-100 peptide. The antiviral peptides of P9R Peptide 3, M1 peptide 1 and P9 Peptide 3 with p=0.029, p<0.05 significant ( -192.321Kcal/mol), p=0.918, p>0.05 insignificant (-179.685Kcal/ mol), p=0.029 p<0.05 significant (-172.523Kcal/mol) showed better results in comparison to reference Macrocyclic iHA-100 peptide ( -207.052 Kcal/mol). Conclusion: The identified novel antiviral peptides could effectively inhibit gp41 protein than other drugs in the market to treat AIDS(acquired immunodeficiency syndrome) disease.
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Wikandari, Prima Retno, and Lenny Yuanita. "PENGARUH DEGRADASI ENZIM PROTEOLITIK TERHADAP AKTIVITAS ANGIOTENSIN CONVERTING ENZYME INHIBITOR BEKASAM DENGAN Lactobacillus plantarum B1765 (The Effect of Degradation of Proteolitic Enzyme on Angiotensin Converting Enzyme Inhibitor Activity of Bekasam with Lactobacillus plantarum B1765)." Jurnal Agritech 36, no. 02 (October 11, 2016): 170. http://dx.doi.org/10.22146/agritech.12861.
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This research studied the effect of digestive enzyme degradation on the Angiotensin Converting Enzyme Inhibitor (ACEI) activity and the stability of bekasam peptide and ACEI activity. Water extract of bekasam was subjected to pepsin and trypsin. The stability of peptide was measured from the changes of peptide concentration before and after treatment by those enzymes. The stability of ACEI activity was measured by hypuric acid liberated from Hip-His-Leu as ACE substrate and determined by spectrophotometer. The results showed that proteolytic enzyme degradation did not affect the concentration of peptide (p>0,05) and the mean concentration 36.72. It was closely related with the ACEI activity that did not change significantly before and after digestion by pepsin and trypsin (p>0,05) and the mean ACEI activity was 70.73. It showed that ACEI activity of bekasam did not change by the degradation of digestive enzyme.Keywords: bekasam, fermented fish, peptides, ACEI activityABSTRAKPenelitian ini bertujuan untuk mengkaji pengaruh degradasi enzim pencernaan proteolitik terhadap stabilitas peptida dan aktivitas Angiotensin Converting Enzyme Inhibitor (ACEI) bekasam yang difermentasi dengan kultur starter Lactobacillus plantarum B1765. Terhadap ekstrak bekasam diberi perlakuan enzim proteolitik pepsin dan tripsin. Pengujian stabilitas peptida diukur dengan ada tidaknya perubahan jumlah peptida setelah perlakuan enzim menggunakan metode formol, sedangkan aktivitas ACEI dilakukan dengan mengetahui jumlah asam hipurat dari substrat Hip-His-Leu yang dibebaskan oleh ACE diukur dengan spektrofotometer. Hasil pengujian menunjukkan perlakuan enzim proteolitik tidak berpengaruh pada konsentrasi peptida dengan p>0,05 dengan nilai rata-rata konsentrasi peptida sebesar 36,72. Hal ini berkorelasi dengan aktivitas ACEI yang juga menunjukkan tidak ada pengaruh antara perlakuan sebelum dan setelah degradasi enzim (p>0,05) dengan rata-rata aktivitas ACEI sebesar 70,73. Hasil penelitian ini menunjukkan bahwa aktivitas ACEI bekasam tidak berubah jika mengalami degradasi enzim pencernaan.Kata kunci: Bekasam, fermentasi ikan, peptida, ACE inhibitor
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Lin, Wen-Wei, Yu-Jen Wang, Cheng-Wen Ko, Tain-Lu Cheng, and Yeng-Tseng Wang. "Cyclic Peptide Inhibitors of the Tsg101 UEV Protein Interactions Refined through Global Docking and Gaussian Accelerated Molecular Dynamics Simulations." Polymers 12, no. 10 (September 28, 2020): 2235. http://dx.doi.org/10.3390/polym12102235.
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Tsg101 UEV domain proteins are potential targets for virus infection therapy, especially for HIV and Ebola viruses. Peptides are key in curbing virus transmission, and cyclic peptides have a greater survival time than their linear peptides. To date, the accurate prediction of cyclic peptide-protein receptors binding conformations still is challenging because of high peptide flexibility. Here, a useful approach combined the global peptide docking, Gaussian accelerated molecular dynamics (GaMD), two-dimensional (2D) potential of mean force (PMF), normal molecular dynamics (cMD), and solvated interaction energy (SIE) techniques. Then we used this approach to investigate the binding conformations of UEV domain proteins with three cyclic peptides inhibitors. We reported the possible cyclic peptide-UEV domain protein binding conformations via 2D PMF free energy profiles and SIE free energy calculations. The residues Trp145, Tyr147, and Trp148 of the native cyclic peptide (CP1) indeed play essential roles in the cyclic peptides-UEV domain proteins interactions. Our findings might increase the accuracy of cyclic peptide-protein conformational prediction, which may facilitate cyclic peptide inhibitor design. Our approach is expected to further aid in addressing the challenges in cyclic peptide inhibitor design.
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Haynes, B. F., L. O. Arthur, P. Frost, T. J. Matthews, A. J. Langlois, T. J. Palker, M. K. Hart, R. M. Scearce, D. M. Jones, and C. McDanal. "Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein." Journal of Experimental Medicine 177, no. 3 (March 1, 1993): 717–27. http://dx.doi.org/10.1084/jem.177.3.717.
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The fusogenic (F) domain of human immunodeficiency virus (HIV) gp41 envelope (env) protein has sequence similarities to many virus and mediates the fusion of HIV-infected cells. During a survey of the immunogenicity of HIV env peptides in chimpanzees, we have observed that HIV peptide immunogenicity was dramatically altered by the NH2-terminal synthesis of the gp41 F domain to an otherwise immunogenic peptide. We compared two hybrid peptide types comprised of T helper (Th) and B cell epitopes of HIV gp120 env protein for their immunogenicity in chimpanzees. The Th-B epitope hybrid peptides contained the HIV gp120 Th cell determinant, T1 (amino acids [aa] 428-440)-synthesized NH2 terminal to gp120 V3 loop peptides, which contain B cell epitopes that induce anti-HIV-neutralizing antibodies (SP10IIIB [aa 303-321] and SP10IIIB [A] [aa 303-327]). The F-Th-B peptide contained the HIV gp41 F domain of HIVIIIB gp41 (aa 519-530)-synthesized NH2 terminal to the Th-B peptide. Whereas Th-B peptides were potent immunogens for chimpanzee antibody and T cell-proliferative responses, the F-Th-B peptide induced lower anti-HIV gp120 T and B cell responses. Moreover, immunization of chimpanzees with F-Th-B peptide but not Th-B peptides induced a significant decrease in peripheral blood T lymphocytes (mean decrease during immunization, 52%; p < 0.02). Chimpanzees previously immunized with F-Th-B peptide did not respond well to immunization with Th-B peptide with T or B cell responses to HIV peptides, demonstrating that the F-Th-B peptide induced immune hyporesponsiveness to Th and B HIV gp120 env determinants. These observations raise the hypothesis that the HIV gp41 env F domain may be a biologically active immunoregulatory peptide in vivo, and by an as yet uncharacterized mechanism, promotes primate immune system hyporesponsiveness to otherwise immunogenic peptides.
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Xiao, Yu-Feng, Meng-Meng Jie, Bo-Sheng Li, Chang-Jiang Hu, Rui Xie, Bo Tang, and Shi-Ming Yang. "Peptide-Based Treatment: A Promising Cancer Therapy." Journal of Immunology Research 2015 (2015): 1–13. http://dx.doi.org/10.1155/2015/761820.
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Many new therapies are currently being used to treat cancer. Among these new methods, chemotherapy based on peptides has been of great interest due to the unique advantages of peptides, such as a low molecular weight, the ability to specifically target tumor cells, and low toxicity in normal tissues. In treating cancer, peptide-based chemotherapy can be mainly divided into three types, peptide-alone therapy, peptide vaccines, and peptide-conjugated nanomaterials. Peptide-alone therapy may specifically enhance the immune system’s response to kill tumor cells. Peptide-based vaccines have been used in advanced cancers to improve patients’ overall survival. Additionally, the combination of peptides with nanomaterials expands the therapeutic ability of peptides to treat cancer by enhancing drug delivery and sensitivity. In this review, we mainly focus on the new advances in the application of peptides in treating cancer in recent years, including diagnosis, treatment, and prognosis.
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Krco, C. J., J. Pawelski, J. Harders, D. McCormick, M. Griffiths, H. S. Luthra, and C. S. David. "Characterization of the antigenic structure of human type II collagen." Journal of Immunology 156, no. 8 (April 15, 1996): 2761–68. http://dx.doi.org/10.4049/jimmunol.156.8.2761.
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Abstract A series of 101 peptides each 20 amino acids in length (10-residue overlap) spanning the helical portion of the mature alpha-chain of human type II collagen (CII) was synthesized. DBA/1 (H-2q) mice were immunized with individual peptides, and draining lymph node cells were challenged in vitro. Strong responses were measured to three peptides: peptide I (residues 74-93), peptide 14 (residues 254-273), and peptide 81 (residues 924-943). B10.Q (H-2q) mice were responsive to peptides I and 81 but not to peptide 14. B10.RIII (H-2r) mice, which are resistant to arthritis induction following immunization with human CII, were unresponsive to peptides I, 14, and 81. Using single amino acid truncated peptides, we determined minimal immunostimulatory lengths for peptides I and 81. Residues critical to antigenicity were identified by introducing alanine and glycine substitutions into minimal length immunostimulatory peptides. The determinants within peptides I and 81 are 100% homologous to mouse CII and are autoantigens. Peptide 81 has homology to viral proteins. Peptide 14 is 90% homologous to mouse CII and has homology to heat shock proteins.
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Jenne, Felix, Ivan Berezkin, Frank Tempel, Dimitry Schmidt, Roman Popov, and Alexander Nesterov-Mueller. "Screening for Primordial RNA–Peptide Interactions Using High-Density Peptide Arrays." Life 13, no. 3 (March 15, 2023): 796. http://dx.doi.org/10.3390/life13030796.
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RNA–peptide interactions are an important factor in the origin of the modern mechanism of translation and the genetic code. Despite great progress in the bioinformatics of RNA–peptide interactions due to the rapid growth in the number of known RNA–protein complexes, there is no comprehensive experimental method to take into account the influence of individual amino acids on non-covalent RNA–peptide bonds. First, we designed the combinatorial libraries of primordial peptides according to the combinatorial fusion rules based on Watson–Crick mutations. Next, we used high-density peptide arrays to investigate the interaction of primordial peptides with their cognate homo-oligonucleotides. We calculated the interaction scores of individual peptide fragments and evaluated the influence of the peptide length and its composition on the strength of RNA binding. The analysis shows that the amino acids phenylalanine, tyrosine, and proline contribute significantly to the strong binding between peptides and homo-oligonucleotides, while the sum charge of the peptide does not have a significant effect. We discuss the physicochemical implications of the combinatorial fusion cascade, a hypothesis that follows from the amino acid partition used in the work.
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Smith, K. D., B. E. Mace, A. Valenzuela, J. L. Vigna, J. A. McCutcheon, J. A. Barbosa, E. Huczko, V. H. Engelhard, and C. T. Lutz. "Probing HLA-B7 conformational shifts induced by peptide-binding groove mutations and bound peptide with anti-HLA monoclonal antibodies." Journal of Immunology 157, no. 6 (September 15, 1996): 2470–78. http://dx.doi.org/10.4049/jimmunol.157.6.2470.
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Abstract To determine the influence of peptide-binding groove residues and MHC-bound peptide on HLA-B7 conformation, we investigated the binding sites of nine locus- or allele-specific mAbs using a panel of 82 HLA-B7 variants. The functional mAb epitopes encircle the HLA-B7 peptide-binding groove. Three mAbs are affected by mutations at solvent-accessible peptide-binding groove mutations. Mutations in peptide-binding groove residues 45, 63, and 150 affect multiple nonoverlapping mAb epitopes, probably by interaction with other MHC residues or bound peptide. However, 18 of 24 peptide-binding groove mutations do not affect mAb binding, indicating that the conformation of solvent-accessible HLA-B7 structures is largely dissociated from changes in the peptide-binding groove. To test whether bound peptides alter HLA-B7 conformation, we loaded HLA-B7 heavy chains on acid-stripped cells with beta2-microglobulin and 20 individual synthetic peptides. Two of eight mAbs are sensitive to HLA-B7-bound peptides. A likely interpretation of these data is that the conformational flexibility of HLA-B7 is due to peptide-induced conformational shifts in MHC side chains, rather than major shifts in the MHC main chain. These results suggest that HLA-B7 conformation is largely maintained in the context of different bound peptides and different peptide-binding grooves.
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Sun, Xiaopeng, Min Wang, Chuanjin Xu, Shanglong Wang, Li Li, Shengcan Zou, Jia Yu, and Yuxi Wei. "Positive Effect of a Pea–Clam Two-Peptide Composite on Hypertension and Organ Protection in Spontaneously Hypertensive Rats." Nutrients 14, no. 19 (September 30, 2022): 4069. http://dx.doi.org/10.3390/nu14194069.
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In the present study, we prepared pea peptides with high angiotensin-converting enzyme (ACE) inhibitory activity in vitro using an enzymatic hydrolysis of pea protein and compounded them with clam peptides to obtain a pea-clam double peptide. The effects of the two-peptide composite and pea peptides on hypertension and the damage-repair of corresponding organs were studied in spontaneously hypertensive rats (SHRs). We found that both pea peptides and the two-peptide composite significantly reduced the blood pressure upon a single or long-term intragastric administration, with the two-peptide composite being more effective. Mechanistically, we found that the two-peptide composite could regulate the renal renin-angiotensin system (RAS), rebalance gut microbial dysbiosis, decrease renal and myocardial fibrosis, and improve renal and cardiac function and vascular remodeling. Additionally, hippocampal lesions caused by hypertension were also eliminated after two-peptide composite administration. Our research provides a scientific basis for the use of this two-peptide composite as a safe antihypertension ingredient in functional foods.
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Reyes-Vargas, Eduardo, Adam P. Barker, Zemin Zhou, Xiao He, and Peter E. Jensen. "HLA–DM senses peptide-MHC class II interactions throughout the peptide binding groove." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 146.22. http://dx.doi.org/10.4049/jimmunol.198.supp.146.22.
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Abstract HLA-DM is an enzyme-like molecule that edits the MHC class II peptide repertoire by catalyzing multiple rounds of peptide exchange on MHCII molecules. It differentially edits peptide-MHCII complexes and thereby skews the foreign and self-peptide repertoire available for activation or tolerance induction of CD4 T-cells. Though it has important implications for the adaptive immune response, the determinants of susceptibility to DM mediated editing remain undefined. It has been suggested that unstable interactions at the N-terminus of a bound peptide is a key determinant for DM editing and that partial dissociation of the peptides N-terminus is necessary for this sensitivity. Herein, we assessed individual components of the catalytic mechanism in real-time kinetic measurements of DM activity. Using a series of amino acid substituted peptides, we analyzed the effects of disfavored interactions on the catalytic turnover and affinity of DM editing and find that disruptions throughout the peptide binding groove contribute to both the affinity of DM for a given peptide complex and to the rate of peptide dissociation from the catalytic complex. Moreover, disruptions in the conserved hydrogen bond network or disfavored amino acid residues near a peptides C-terminus result in increased DM affinity and catalytic turnover. Furthermore, complexes with N-terminal truncated peptides show increased catalytic turnover when compared to parent complexes, indicating that the functionally active DM-peptide-MHCII catalytic complex can operate on a peptide-MHCII complex with full occupancy. Together, this implies that interactions at the DM-MHCII interface are intimately linked to unstable interactions throughout the peptide-binding groove.
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Wang, Qian, Yanhui Wang, Jian Li, Hong Liu, and Shiyu Chen. "Bicyclic peptide-enhanced covalent inhibitor of SARS-CoV-2 3CL protease." Exploration of Drug Science 2, no. 6 (October 17, 2024): 719–33. http://dx.doi.org/10.37349/eds.2024.00071.
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Aim: Develop technology to apply bicyclic peptides for discovering covalent inhibitors of proteases and use this technology to create bicyclic peptide—warhead conjugates for targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like (3CL) protease. Enhance the potency of the discovered bicyclic peptides for potential development into anti-SARS-CoV-2 drugs. Methods: Rational design was employed to discover the initial bicyclic peptide—warhead conjugates. Medicinal chemistry optimization was conducted to improve the potency of these peptides. Enzymatic assays and mass spectrometry characterization were performed to validate the covalent inhibition of the target protease. Results: The need for peptide display selection in discovering hit bicyclic peptides was overcome. Active bicyclic peptide—vinyl sulfone inhibitors with nanomolar potency were discovered. Optimization through medicinal chemistry strategies not only improved the potency of the peptides but also revealed residue preferences at individual positions of the bicyclic peptide inhibitors. The most potent bicyclic peptide can inhibit the target with a half-maximal inhibitory concentration (IC50) of 40.46 ± 6.35 nM. Mass spectrometry tests confirmed the covalent inhibition of the target protease by the developed peptides. Conclusions: Bicyclic peptide and vinyl sulfone conjugates are a form of covalent and potent inhibitors for targeting proteases. The rational design of bicyclic peptide ligands is feasible when structural and amino acid preference information is available. Structural information is also crucial for optimizing the potency of bicyclic peptide ligands.
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Kawada, Tsuyoshi, Michio Ogasawara, Toshio Sekiguchi, Masato Aoyama, Kohji Hotta, Kotaro Oka, and Honoo Satake. "Peptidomic Analysis of the Central Nervous System of the Protochordate, Ciona intestinalis: Homologs and Prototypes of Vertebrate Peptides and Novel Peptides." Endocrinology 152, no. 6 (April 5, 2011): 2416–27. http://dx.doi.org/10.1210/en.2010-1348.
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The phylogenetic position of ascidians as the chordate invertebrates closest to vertebrates suggests that they might possess homologs and/or prototypes of vertebrate peptide hormones and neuropeptides as well as ascidian-specific peptides. However, only a small number of peptides have so far been identified in ascidians. In the present study, we have identified various peptides in the ascidian, Ciona intestinalis. Mass spectrometry-based peptidomic analysis detected 33 peptides, including 26 novel peptides, from C. intestinalis. The ascidian peptides are largely classified into three categories: 1) prototypes and homologs of vertebrate peptides, such as galanin/galanin-like peptide, which have never been identified in any invertebrates; 2) peptides partially homologous with vertebrate peptides, including novel neurotesin-like peptides; 3) novel peptides. These results not only provide evidence that C. intestinalis possesses various homologs and prototypes of vertebrate neuropeptides and peptide hormones but also suggest that several of these peptides might have diverged in the ascidian-specific evolutionary lineage. All Ciona peptide genes were expressed in the neural complex, whereas several peptide gene transcripts were also distributed in peripheral tissues, including the ovary. Furthermore, a Ciona neurotensin-like peptide, C. intestinalis neurotensin-like peptide 6, was shown to down-regulate growth of Ciona vitellogenic oocytes. These results suggest that the Ciona peptides act not only as neuropeptides in the neural tissue but also as hormones in nonneuronal tissues and that ascidians, unlike other invertebrates, such as nematodes, insects, and sea urchins, established an evolutionary origin of the peptidergic neuroendocrine, endocrine, and nervous systems of vertebrates with certain specific molecular diversity.
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Hashim, Shehla, Yuan Li, and Madhu B. Anand-Srivastava. "Small cytoplasmic domain peptides of natriuretic peptide receptor-C attenuate cell proliferation through Giα protein/MAP kinase/PI3-kinase/AKT pathways." American Journal of Physiology-Heart and Circulatory Physiology 291, no. 6 (December 2006): H3144—H3153. http://dx.doi.org/10.1152/ajpheart.00327.2006.
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The present studies were undertaken to investigate the effect of C-atrial natriuretic peptide (ANP)4–23 and several peptide fragments containing 12 amino acids from different regions of the cytoplasmic domain of natriuretic peptide receptor (NPR)-C on cell proliferation in the absence or presence of angiotensin (ANG) II, endothelin (ET)-1, and arginine vasopressin (AVP) in A-10 vascular smooth muscle cells (VSMC). The peptide fragments used have either complete Gi activator sequences K461-H472 (peptide 1) and H481-H492 (peptide 3) or partial Gi activator sequences R469-K480 (peptide 2) and I465-H472 (peptide Y) with truncated COOH or NH2 terminus, respectively. The other peptide used had no structural specificity (Q473-K480, peptide X) or was the scrambled peptide control for peptide 1 (peptide Z). ANG II, ET-1 and AVP significantly stimulated DNA synthesis in these cells as determined by [3H]thymidine incorporation that was inhibited by peptides 1, 2, and 3 and not by peptides X, Y, and Z in a concentration-dependent manner, with an apparent Ki between 1 and 10 nM. In addition, C-ANP4–23, which interacts with NPR-C, also inhibited DNA synthesis stimulated by vasoactive peptides; however, the inhibition elicited by C-ANP4–23 was not additive with the inhibition elicited by peptide 1. On the other hand, basal DNA synthesis in these cells was not inhibited by C-ANP4–23 or the peptide fragments. Furthermore, vasoactive peptide-induced stimulation of DNA synthesis was inhibited by PD-98059 and wortmannin, and this inhibition was potentiated by peptide 1. In addition, peptide 1 also inhibited vasoactive peptide-induced phosphorylation of ERK1/2 and AKT and enhanced expression of Giα proteins. These data suggest that C-ANP4–23 and small peptide fragments containing 12 amino acids irrespective of the region of the cytoplasmic domain of NPR-C inhibit proliferative responses of vasoactive peptides through Giα protein and MAP kinase/phosphatidylinositol 3-kinase/AKT pathways.
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Choppin, J., F. Martinon, E. Gomard, E. Bahraoui, F. Connan, M. Bouillot, and J. P. Lévy. "Analysis of physical interactions between peptides and HLA molecules and application to the detection of human immunodeficiency virus 1 antigenic peptides." Journal of Experimental Medicine 172, no. 3 (September 1, 1990): 889–99. http://dx.doi.org/10.1084/jem.172.3.889.
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The physical association of 40 antigenic peptides and purified HLA class I and class II molecules was monitored using a direct peptide binding assay (PBA) in solid phase and an inhibition peptide binding assay (IPBA) in which the competing peptide was present in a soluble phase. We also examined the ability of different peptides to inhibit the lytic activity of human antiviral cytolytic T cells towards cells incubated with the corresponding target peptide. Our results showed that: (a) Binding of a given human T cell-recognized peptide to several HLA class I and class II molecules occurred frequently. Nevertheless, preferential binding of peptides to their respective restriction molecules was also observed. (b) Binding of HLA molecules to peptides recognized by murine T cells occurred less frequently. (c) 11 of 24 (46%) randomly selected HIV-1 peptides contained agretopic residues allowing their binding to HLA molecules. (d) The kinetics of HLA/peptide association depended on the peptide tested and were faster than or similar to those reported for Ia molecules. Dissociation of these complexes was very low. (e) Peptide/HLA molecule binding was dependent on length, number of positive charges, and presence of hydrophobic residue in the peptide. (f) A correlation was demonstrated between a peptide inhibitory effect in the IPBA and its blocking effect in the cytolytic test. Our data indicated that the restriction phenomenon observed in T cell responses was not strictly related to either an elective HLA/peptide association, or a high binding capacity of a peptide to HLA molecules. These data also showed that the PBA and IPBA are appropriate for the detection of agretopic residues within HIV-1 proteins.
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Wojciechowska, Monika, Joanna Miszkiewicz, and Joanna Trylska. "Conformational Changes of Anoplin, W-MreB1–9, and (KFF)3K Peptides near the Membranes." International Journal of Molecular Sciences 21, no. 24 (December 18, 2020): 9672. http://dx.doi.org/10.3390/ijms21249672.
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Many peptides interact with biological membranes, but elucidating these interactions is challenging because cellular membranes are complex and peptides are structurally flexible. To contribute to understanding how the membrane-active peptides behave near the membranes, we investigated peptide structural changes in different lipid surroundings. We focused on two antimicrobial peptides, anoplin and W-MreB1–9, and one cell-penetrating peptide, (KFF)3K. Firstly, by using circular dichroism spectroscopy, we determined the secondary structures of these peptides when interacting with micelles, liposomes, E. coli lipopolysaccharides, and live E. coli bacteria. The peptides were disordered in the buffer, but anoplin and W-MreB1–9 displayed lipid-induced helicity. Yet, structural changes of the peptide depended on the composition and concentration of the membranes. Secondly, we quantified the destructive activity of peptides against liposomes by monitoring the release of a fluorescent dye (calcein) from the liposomes treated with peptides. We observed that only for anoplin and W-MreB1–9 calcein leakage from liposomes depended on the peptide concentration. Thirdly, bacterial growth inhibition assays showed that peptide conformational changes, evoked by the lipid environments, do not directly correlate with the antimicrobial activity of the peptides. However, understanding the relation between peptide structural properties, mechanisms of membrane disruption, and their biological activities can guide the design of membrane-active peptides.
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Lee, Chong-Kil, Chan-su Park, Sun-A. Im, Young-Jun Park, Jae Hee Lee, and Kyungjae Kim. "Computational prediction and functional identification of HLA-A2-restricted T lymphocyte epitopes derived from swine leukocyte antigen (TRAN2P.962)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 209.2. http://dx.doi.org/10.4049/jimmunol.194.supp.209.2.
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Abstract Xenotransplantation using porcine organs is a potential solution to the problem of the shortage of allografts. However, immunological rejection of xenografts remains as a major hurdle to success. Little information is available regarding the precise swine leukocyte antigen (SLA)-derived immunogenic peptides that are presented in the context of human HLA molecules. The SLA-derived peptides that bind to HLA-A*0201, a representative of the A2 supertype, were predicted using a computer-assisted algorithm. The candidate peptides were synthesized, and the stabilities of complexes formed between the peptides and HLA-A*0201 were compared using MHC stabilization assays. The cytotoxic T lymphocyte (CTL)-inducing activity of the selected peptides was examined in HLA-A*0201-transgenic mice. Among 15 candidate peptides synthesized, two peptides, peptide-35 (YLGPDGLLL) and peptide-43 (TLICHVDSI), were selected to have high affinity and stability with HLA-A*0201. Examination of the CTL-inducing activity of the two peptides in HLA-A*0201-transgenic mice showed that immunization with peptide-35, but not peptide-43, elicited potent CD8-specific-CTL responses. The Peptide-35 is present in non-polymorphic a2 domains of 34 SLA-1 alleles, 18 SLA-2 alleles, and 1 SLA-3 allele. These results show that Peptide-35 is a HLA-A2-restricted immunogenic peptide derived from SLA.
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Sergeyev, O. V., and I. F. Barinsky. "Synthetic peptide vaccines." Problems of Virology 61, no. 1 (February 28, 2016): 5–8. http://dx.doi.org/10.18821/0507-4088-2016-61-1-5-8.
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An update on the development and trials of synthetic peptide vaccines is reviewed. The review considers the successful examples of specific protection as a result of immunization with synthetic peptides using various protocols. The importance of conformation for the immunogenicity of the peptide is pointed out. An alternative strategy of the protection of the organism against the infection using synthetic peptides is suggested.
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Martin, Aline, Valentin David, Jennifer S. Laurence, Patricia M. Schwarz, Eileen M. Lafer, Anne-Marie Hedge, and Peter S. N. Rowe. "Degradation of MEPE, DMP1, and Release of SIBLING ASARM-Peptides (Minhibins): ASARM-Peptide(s) Are Directly Responsible for Defective Mineralization in HYP." Endocrinology 149, no. 4 (December 27, 2007): 1757–72. http://dx.doi.org/10.1210/en.2007-1205.
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Mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) and DMP1 (dentin matrix protein 1) result in X-linked hypophosphatemic rickets (HYP) and autosomal-recessive hypophosphatemic-rickets (ARHR), respectively. Specific binding of PHEX to matrix extracellular phosphoglycoprotein (MEPE) regulates the release of small protease-resistant MEPE peptides [acidic serine- and aspartate-rich MEPE-associated motif (ASARM) peptides]. ASARM peptides are potent inhibitors of mineralization (minhibins) that also occur in DMP1 [MEPE-related small integrin-binding ligand, N-linked glycoprotein (SIBLING) protein]. It is not known whether these peptides are directly responsible for the mineralization defect. We therefore used a bone marrow stromal cell (BMSC) coculture model, ASARM peptides, anti-ASARM antibodies, and a small synthetic PHEX peptide (SPR4; 4.2 kDa) to examine this. Surface plasmon resonance (SPR) and two-dimensional 1H/15N nuclear magnetic resonance demonstrated specific binding of SPR4 peptide to ASARM peptide. When cultured individually for 21 d, HYP BMSCs displayed reduced mineralization compared with wild type (WT) (−87%, P < 0.05). When cocultured, both HYP and WT cells failed to mineralize. However, cocultures (HYP and WT) or monocultures of HYP BMSCs treated with SPR4 peptide or anti-ASARM neutralizing antibodies mineralized normally. WT BMSCs treated with ASARM peptide also failed to mineralize properly without SPR4 peptide or anti-ASARM neutralizing antibodies. ASARM peptide treatment decreased PHEX mRNA and protein (−80%, P < 0.05) and SPR4 peptide cotreatment reversed this by binding ASARM peptide. SPR4 peptide also reversed ASARM peptide-mediated changes in expression of key osteoclast and osteoblast differentiation genes. Western blots of HYP calvariae and BMSCs revealed massive degradation of both MEPE and DMP1 protein compared with the WT. We conclude that degradation of MEPE and DMP-1 and release of ASARM peptides are chiefly responsible for the HYP mineralization defect and changes in osteoblast-osteoclast differentiation.
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Attiyah, Sama M., Alexandra Bermudez-Fajardo, and Ernesto Oviedo-Orta. "A proteomics study of MHC-associated peptide profiles displayed by macrophages after stimulation in vitro with human low density lipoproteins (78.12)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 78.12. http://dx.doi.org/10.4049/jimmunol.182.supp.78.12.
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Abstract Recognition of modified self proteins by macrophages usually induces the generation of peptide fragments derived cytoplasmic pool of cells that can be presented by the major histocompatibility complex (MHC). Despite the potential for presentation of a wide range of peptides only a limited number of peptides are displayed by the complexes. This generates peptide patterns that imprint a signature associated with particular cellular or disease processes. The aim of this study was to investigate whether stimulation of macrophages with human low density lipoprotein (LDL) generates peptide patterns on macrophage MHC class I and II in vitro. The study also assessed the effectiveness of peptide elution methods for peptide extraction. To accomplish this we stimulated J774.2 cells with native or oxidised LDL particles and extracted the MHC-associated peptides using citrate-phosphate buffer at pH 3, 4 & 5. Samples were then analysed by LC/MS/MS. MASCOT analysis was carried out to identify the protein source of peptides and IEDB and NetMHCII 1.0 were used to predict the peptide-binding affinity to MHC class I and II complexes. We identified 54 peptides derived from macrophages stimulated with ox-LDL, 33 peptides derived from cells treated with n-LDL and 10 peptides identified from untreated cells. Peptide derived from proteins involved in macrophage DNA and RNA replication, signal transduction, cytoskeleton and lipid metabolism were identified. We found a differential pattern of MHC-associated peptide expression in treated macrophages. These findings contribute to future identification of disease-associated peptides for their potential use in the development of therapeutic and/or diagnostic tools.
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Shimojo, N., W. L. Maloy, R. W. Anderson, W. E. Biddison, and J. E. Coligan. "Specificity of peptide binding by the HLA-A2.1 molecule." Journal of Immunology 143, no. 9 (November 1, 1989): 2939–47. http://dx.doi.org/10.4049/jimmunol.143.9.2939.
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Abstract The HLA-A2 molecule contains a putative peptide binding site that is bounded by two alpha-helices and a beta-pleated sheet floor. Previous studies have demonstrated that the influenza virus matrix peptide M1 55-73 can sensitize target cells for lysis by HLA-A2.1-restricted virus-immune CTL and can induce CTL that can lyse virus-infected target cells. To assess the specificity of peptide binding by the HLA-A2.1 molecule, we examined the ability of seven variant M1 peptides to be recognized by a panel of M1 55-73 peptide-specific HLA-A2.1-restricted CTL lines. The results demonstrate that five out of the seven variant M1 55-73 peptides could be recognized by A2.1-restricted M1 55-73 peptide-specific CTL lines. The two variant peptides that were not recognized by any CTL could bind to HLA-A2.1 as indicated by their ability to compete for presentation of the M1 55-73 peptide. In addition, 5 of a panel of 24 unrelated peptides tested could also compete for M1 55-73 presentation by HLA-A2.1. One peptide derived from the sequence of a rotavirus protein could sensitize HLA-A2.1+ targets for lysis by M1 55-73 peptide-specific CTL. We conclude from these studies that: 1) the HLA-A2.1 molecule can bind a broad spectrum of peptides; 2) T cells selected for the ability to recognize one peptide plus a class I molecule can actually recognize an unrelated peptide presented by that same class I molecule; and 3) a stretch of three adjacent hydrophobic amino acids may be an important common feature of peptides that can bind to HLA-A2.1.
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Forouharmehr, Ali, Nemat Shams, Narges Nazifi, Amin Jaydari, and Ehsan Rashidian. "Prediction of an Efficient Signal Peptide for Optimized Expression of Mycobacterium Tuberculosis Heparin-binding Hemagglutinin Gene in Periplasmic Compartment of Escherichia Coli: A Bioinformatics Investigation." Journal of Inflammatory Diseases 26, no. 1 (March 1, 2022): 9–18. http://dx.doi.org/10.32598/jid.26.1.4.
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Background: The heparin-binding hemagglutinin (HBHA) protein belonging to Mycobacterium tuberculosis is known as a molecular adjuvant. Objective: Hence, the expression of this protein in the prokaryotic system is essential. Methods: To predict an appropriate signal peptide for the expression of the HBHA protein, 50 signal peptides were selected from the signal peptide database. Then, the crucial parameters of signal peptides, including the probability of signal peptide, different regions of signal peptides, physicochemical features, sorting of signal peptides, and sub-cellular location were completely investigated by reliable tools. After the best-predicted signal peptide was identified, it was linked to the HBHA protein, and its secondary structure, tertiary structure, and in silico cloning in pET21a (+) was assessed. Findings: The results of different evaluations confirmed that only 13 signal peptides passed all features, including clearance of N, H, and C regions, D-score >0.7, instability index >40, and periplasmic localization. Finally, based on D-scores, among these 13 signal peptides, the asr (acid shock RNA) peptide with D-score=90 was selected as the best-predicted signal peptide to apply. Moreover, the results showed that the secondary structure of the adjuvant linked to asr peptide contained 88.18% alpha helix and 9.5% random coil. Also, the results of in silico cloning showed that the nucleotide sequences of the adjuvant linked to the asr peptide were successfully cloned between BamHI and XhoI enzymes in the multiple cloning site of pET21a (+). Conclusion: The results of this study confirmed that the asr peptide can be used as an appropriate signal peptide for the expression of the HBHA protein in the prokaryotic system.
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Pimont-Farge, Mathilde, Amélie Bérubé, Véronique Perreault, Guillaume Brisson, Shyam Suwal, Yves Pouliot, and Alain Doyen. "Occurrence of Peptide-Peptide Interactions during the Purification of Self-Assembling Peptide f1-8 from a β-Lactoglobulin Tryptic Hydrolysate." Molecules 26, no. 5 (March 6, 2021): 1432. http://dx.doi.org/10.3390/molecules26051432.
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Self-assembling peptides have gained attention because of their nanotechnological applications. Previous work demonstrated that the self-assembling peptide f1-8 (Pf1-8) that is generated from the tryptic hydrolysis of β-lactoglobulin can form a hydrogel after several purification steps, including membrane filtration and consecutive washes. This study evaluates the impact of each processing step on peptide profile, purity, and gelation capacity of each fraction to understand the purification process of Pf1-8 and the peptide-peptide interactions involved. We showed that peptide-peptide interactions mainly occurred through electrostatic and hydrophobic interactions, influencing the fraction compositions. Indeed, the purity of Pf1-8 did not correlate with the number of wash steps. In addition to Pf1-8, two other hydrophobic peptides were identified, peptide f15-20, and peptide f41-60. The gelation observed could be induced either through peptide-peptide interactions or through self-assembling, both being driven by non-covalent bond and more specifically hydrophobic interactions.
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Skipper, J. C., R. C. Hendrickson, P. H. Gulden, V. Brichard, A. Van Pel, Y. Chen, J. Shabanowitz, et al. "An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins." Journal of Experimental Medicine 183, no. 2 (February 1, 1996): 527–34. http://dx.doi.org/10.1084/jem.183.2.527.
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T lymphocytes recognize antigens consisting of peptides presented by class I and II major histocompatibility complex (MHC) molecules. The peptides identified so far have been predictable from the amino acid sequences of proteins. We have identified the natural peptide target of a CTL clone that recognizes the tyrosinase gene product on melanoma cells. The peptide results from posttranslational conversion of asparagine to aspartic acid. This change is of central importance for peptide recognition by melanoma-specific T cells, but has no impact on peptide binding to the MHC molecule. This posttranslational modification has not been previously described for any MHC-associated peptide and represents the first demonstration of posttranslational modification of a naturally processed class I-associated peptide. This observation is relevant to the identification and prediction of potential peptide antigens. The most likely mechanism for production of this peptide leads to the suggestion that antigenic peptides can be derived from proteins that are translated into the endoplasmic reticulum.
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Asghari Baghkheirati, Amir, Elnaz Karbaschian, Seyedah Zahra Mousavi, and Mohammad Hadi Sekhavati. "Prediction of the best signal peptide for periplasmic expression of melittin peptide in Escherichia coli." Journal of Poultry Sciences and Avian Diseases 2, no. 2 (2024): 50–55. http://dx.doi.org/10.61838/kman.jpsad.2.2.6.
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Periplasmic expression of antimicrobial peptides is one of the most important issues in cloning and protein expression systems. In the present study, bioinformatics methods were used to predict the best signal peptides for periplasmic expression of the melittin peptide in Escherichia coli. Therefore, the sequence of 12 signal peptides was prepared from signal peptide databases. In order to choose the best signal peptide, periplasmic expression, sub-cellular localization site, solubility, physical, and chemical properties of signal peptides were analyzed by Signalp6, Psort, Protein-sol, PRED-TAT, and Portparam servers. Out of 12 signal peptides, six passed the Signalp6 filter, and only two passed Psort. After examining the solubility of signal peptides and investigating their physical and chemical properties, it was determined that zraP has the most favorable characteristics. Finally, it can be concluded that zraP could be considered as the best signal peptide for the melittin expression. Our results can be used for periplasmic expression of melittin in Escherichia coli host.
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Li, Caroline M., Pouya Haratipour, Robert G. Lingeman, J. Jefferson P. Perry, Long Gu, Robert J. Hickey, and Linda H. Malkas. "Novel Peptide Therapeutic Approaches for Cancer Treatment." Cells 10, no. 11 (October 27, 2021): 2908. http://dx.doi.org/10.3390/cells10112908.
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Peptides are increasingly being developed for use as therapeutics to treat many ailments, including cancer. Therapeutic peptides have the advantages of target specificity and low toxicity. The anticancer effects of a peptide can be the direct result of the peptide binding its intended target, or the peptide may be conjugated to a chemotherapy drug or radionuclide and used to target the agent to cancer cells. Peptides can be targeted to proteins on the cell surface, where the peptide–protein interaction can initiate internalization of the complex, or the peptide can be designed to directly cross the cell membrane. Peptides can induce cell death by numerous mechanisms including membrane disruption and subsequent necrosis, apoptosis, tumor angiogenesis inhibition, immune regulation, disruption of cell signaling pathways, cell cycle regulation, DNA repair pathways, or cell death pathways. Although using peptides as therapeutics has many advantages, peptides have the disadvantage of being easily degraded by proteases once administered and, depending on the mode of administration, often have difficulty being adsorbed into the blood stream. In this review, we discuss strategies recently developed to overcome these obstacles of peptide delivery and bioavailability. In addition, we present many examples of peptides developed to fight cancer.
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Neisig, A., J. Roelse, A. J. Sijts, F. Ossendorp, M. C. Feltkamp, W. M. Kast, C. J. Melief, and J. J. Neefjes. "Major differences in transporter associated with antigen presentation (TAP)-dependent translocation of MHC class I-presentable peptides and the effect of flanking sequences." Journal of Immunology 154, no. 3 (February 1, 1995): 1273–79. http://dx.doi.org/10.4049/jimmunol.154.3.1273.
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Abstract The MHC-encoded transporter associated with Ag presentation (TAP) translocates peptides from the cytosol to the ER lumen, where association with MHC class I molecules occurs. The MHC class I/peptide complex is subsequently transported to the cell surface for presentation to CD8+T cells. We studied TAP-dependent translocation of defined MHC class I presentable murine peptides by competition for translocation of a radiolabeled model peptide, to address whether efficient peptide presentation by MHC class I molecules is preceded by equal efficient peptide translocation by TAP. Surprisingly, we observed that four immunodominant viral peptides of 16 peptides tested were very inefficiently transported by TAP. Inefficient translocation could be overcome by substitution of a proline residue present at position 3 in the peptides. Furthermore, addition of natural flanking amino acids directly surrounding a poorly transported peptide could considerably improve translocation by TAP. Our data suggest that some peptides are efficiently transported by TAP in their optimal size for MHC class I binding, whereas other peptides are transported as larger peptide fragments that need further trimming in the ER for MHC class I binding.
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Harig, Sabine, Mathias Witzens, Angela M. Krackhardt, Andreas Trojan, Patrick Barrett, Ryan Broderick, A. Jason Zauls, and John G. Gribben. "Induction of cytotoxic T-cell responses against immunoglobulin V region–derived peptides modified at human leukocyte antigen–A2 binding residues." Blood 98, no. 10 (November 15, 2001): 2999–3005. http://dx.doi.org/10.1182/blood.v98.10.2999.
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Abstract Cytotoxic T-lymphocyte (CTL) responses can be generated against peptides derived from the immunoglobulin (Ig) V region in some but not all patients. The main reason for this appears to be the low peptide-binding affinity of Ig-derived peptides to major histocompatibility complex (MHC) class I molecules and their resulting low immunogenicity. This might be improved by conservative amino acid modifications at the MHC-binding residues of the peptides (heteroclitic peptides). In this study, it was found that in 18 Ig-derived peptides, that heteroclitic peptides from the Ig gene with improved binding to human leukocyte antigen (HLA)-A*0201 can be used to improve CTL responses. Amino acid substitution substantially increased predicted binding affinity, and there was a strong correlation between predicted and actual binding to HLA-A*0201. CTLs generated against the heteroclitic peptide had not only enhanced cytotoxicity against the heteroclitic peptide but also increased killing of antigen-presenting cells pulsed with the native peptide. Surprisingly, no difference was observed in the frequency of T cells detected by MHC class I peptide tetramers after stimulation with the heteroclitic peptide compared with the native peptide. CTLs generated against heteroclitic peptides could kill patients' tumor cells, showing that Ig-derived peptides can be presented by the tumor cell and that the failure to mount an immune response (among other reasons) likely results from the low immunogenicity of the native Ig-derived peptide. These results suggest that heteroclitic Ig-derived peptides can enhance immunogenicity, thereby eliciting immune responses, and that they might be useful tools for enhancing immunotherapy approaches to treating B-cell malignant diseases.
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Fujii, Daisuke, Kento Takase, Ami Takagi, Kei Kamino, and Yoshiaki Hirano. "Design of RGDS Peptide-Immobilized Self-Assembling β-Strand Peptide from Barnacle Protein." International Journal of Molecular Sciences 22, no. 3 (January 27, 2021): 1240. http://dx.doi.org/10.3390/ijms22031240.
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We designed three types of RGD-containing barnacle adhesive proteins using self-assembling peptides. In the present study, three types of RGD-containing peptides were synthesized by solid-phase peptide synthesis, and the secondary structures of these peptides were analyzed by CD and FT-IR spectroscopy. The mechanical properties of peptide hydrogels were characterized by a rheometer. We discuss the correlation between the peptide conformation, and cell attachment and cell spreading activity from the viewpoint of developing effective tissue engineering scaffolds. We created a peptide-coated cell culture substrate by coating peptides on a polystyrene plate. They significantly facilitated cell adhesion and spreading compared to a non-coated substrate. When the RGDS sequence was modified at N- or C-terminal of R-Y, it was found that the self-assembling ability was dependent on the strongly affects hydrogel formation and cell adhesion caused by its secondary structure.
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Saeed, Mesha, Erik Schooten, Mandy van Brakel, David K. Cole, Timo L. M. ten Hagen, and Reno Debets. "T Cells Expressing a TCR-Like Antibody Selected Against the Heteroclitic Variant of a Shared MAGE-A Epitope Do Not Recognise the Cognate Epitope." Cancers 12, no. 5 (May 16, 2020): 1255. http://dx.doi.org/10.3390/cancers12051255.
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Antibodies-recognising peptides bound to the major histocompatibility complex (pMHC) represent potentially valuable and promising targets for chimeric antigen receptor (CAR) T cells to treat patients with cancer. Here, a human phage-Fab library has been selected using HLA-A2 complexed with a heteroclitic peptide variant from an epitope shared among multiple melanoma-associated antigens (MAGEs). DNA restriction analyses and phage ELISAs confirmed selection of unique antibody clones that specifically bind to HLA-A2 complexes or HLA-A2-positive target cells loaded with native or heteroclitic peptide. Antibodies selected against heteroclitic peptide, in contrast to native peptide, demonstrated significantly lower to even negligible binding towards native peptide or tumour cells that naturally expressed peptides. The binding to native peptide was not rescued by phage panning with antigen-positive tumour cells. Importantly, when antibodies directed against heteroclitic peptides were engineered into CARs and expressed by T cells, binding to native peptides and tumour cells was minimal to absent. In short, TCR-like antibodies, when isolated from a human Fab phage library using heteroclitic peptide, fail to recognise its native peptide. We therefore argue that peptide modifications to improve antibody selections should be performed with caution as resulting antibodies, either used directly or as CARs, may lose activity towards endogenously presented tumour epitopes.
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Edwards-Gayle, Charlotte J. C., and Ian W. Hamley. "Self-assembly of bioactive peptides, peptide conjugates, and peptide mimetic materials." Organic & Biomolecular Chemistry 15, no. 28 (2017): 5867–76. http://dx.doi.org/10.1039/c7ob01092c.
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Self-assembling peptide and peptide conjugates have attracted great attention due to their biocompatibility, biodegradability and biofunctionality. This review covers self-assembly of amphiphilic peptides and peptide mimetic materials, as well as their potential applications.