Journal articles: 'Synthetic Self-assembling Amino Acid'

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Lesiak, Marta, Aleksandra Augusciak-Duma, Anna Szydlo, Ksymena Pruszczynska, and Aleksander L. Sieron. "Specific inhibition of procollagen C-endopeptidase activity by synthetic peptide with conservative sequence found in chordin." Acta Biochimica Polonica 55, no. 2 (June 7, 2008): 297–305. http://dx.doi.org/10.18388/abp.2008_3076.

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Procollagen C-endopeptidase (BMP-1) and N-endopeptidase (ADAMTS-2) are key enzymes for correct and efficient conversion of fibrillar procollagens to their self assembling monomers. Thus, they have an essential role in building and controlling the quality of extracellular matrices (ECMs). Here, we tested inhibition of activity of the largest variant of BMP-1, a recombinant mammalian tolloid (mTld), in vitro by three synthetic peptides with conservative amino-acid sequences found in chordin using procollagen type I as a substrate. We also verified the specific action of best inhibitory 16 amino-acid peptide in the procollagen type I cleavage assay with the use of ADAMTS-2 (procollagen N-endopeptidase). Subsequently, we determined the critical residues and minimal sequence of six amino acids in the original 16 amino-acid peptide required to maintain the inhibitory potential. Studies on the interactions of 6 and 16 amino acid long peptides with the enzyme revealed their binding to non-catalytic, regulatory domains of mTld; the inhibitory activity was not due to the competition of peptides with the substrate for the enzyme active center, because mTld did not cleave the peptides. However, in the presence of mTld both peptides underwent cyclization by disulfide bond formation. Concluding, we have shown that procollagen C-endopeptidase may be specifically blocked via its non-catalytic domains by synthetic peptide consisting of 6 amino acids in the sequence found in highly conservative region of chordin. Thus, we hypothesize that the 6 amino-acid peptide could be a good candidate for anti-fibrotic drug development.

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Gaynanova, Gulnara, Leysan Vasileva, Ruslan Kashapov, Darya Kuznetsova, Rushana Kushnazarova, Anna Tyryshkina, Elmira Vasilieva, Konstantin Petrov, Lucia Zakharova, and Oleg Sinyashin. "Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability." Molecules 26, no. 22 (November 10, 2021): 6786. http://dx.doi.org/10.3390/molecules26226786.

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This review focuses on key topics in the field of drug delivery related to the design of nanocarriers answering the biomedicine criteria, including biocompatibility, biodegradability, low toxicity, and the ability to overcome biological barriers. For these reasons, much attention is paid to the amphiphile-based carriers composed of natural building blocks, lipids, and their structural analogues and synthetic surfactants that are capable of self-assembly with the formation of a variety of supramolecular aggregates. The latter are dynamic structures that can be used as nanocontainers for hydrophobic drugs to increase their solubility and bioavailability. In this section, biodegradable cationic surfactants bearing cleavable fragments are discussed, with ester- and carbamate-containing analogs, as well as amino acid derivatives received special attention. Drug delivery through the biological barriers is a challenging task, which is highlighted by the example of transdermal method of drug administration. In this paper, nonionic surfactants are primarily discussed, including their application for the fabrication of nanocarriers, their surfactant-skin interactions, the mechanisms of modulating their permeability, and the factors controlling drug encapsulation, release, and targeted delivery. Different types of nanocarriers are covered, including niosomes, transfersomes, invasomes and chitosomes, with their morphological specificity, beneficial characteristics and limitations discussed.

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Tinajero-Díaz, E., A. Martínez de Ilarduya, B. Cavanagh, A. Heise, and S. Muñoz-Guerra. "Poly(amino acid)-grafted polymacrolactones. Synthesis, self-assembling and ionic coupling properties." Reactive and Functional Polymers 143 (October 2019): 104316. http://dx.doi.org/10.1016/j.reactfunctpolym.2019.104316.

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Liu, Renjie, and Gregory A. Hudalla. "Using Self-Assembling Peptides to Integrate Biomolecules into Functional Supramolecular Biomaterials." Molecules 24, no. 8 (April 12, 2019): 1450. http://dx.doi.org/10.3390/molecules24081450.

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Throughout nature, self-assembly gives rise to functional supramolecular biomaterials that can perform complex tasks with extraordinary efficiency and specificity. Inspired by these examples, self-assembly is increasingly used to fabricate synthetic supramolecular biomaterials for diverse applications in biomedicine and biotechnology. Peptides are particularly attractive as building blocks for these materials because they are based on naturally derived amino acids that are biocompatible and biodegradable; they can be synthesized using scalable and cost-effective methods, and their sequence can be tailored to encode formation of diverse architectures. To endow synthetic supramolecular biomaterials with functional capabilities, it is now commonplace to conjugate self-assembling building blocks to molecules having a desired functional property, such as selective recognition of a cell surface receptor or soluble protein, antigenicity, or enzymatic activity. This review surveys recent advances in using self-assembling peptides as handles to incorporate biologically active molecules into supramolecular biomaterials. Particular emphasis is placed on examples of functional nanofibers, nanovesicles, and other nano-scale structures that are fabricated by linking self-assembling peptides to proteins and carbohydrates. Collectively, this review highlights the enormous potential of these approaches to create supramolecular biomaterials with sophisticated functional capabilities that can be finely tuned to meet the needs of downstream applications.

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Rosselin, Marie, Grégory Meyer, Pierre Guillet, Thomas Cheviet, Guillaume Walther, Annette Meister, Dimitra Hadjipavlou-Litina, and Grégory Durand. "Divalent Amino-Acid-Based Amphiphilic Antioxidants: Synthesis, Self-Assembling Properties, and Biological Evaluation." Bioconjugate Chemistry 27, no. 3 (February 22, 2016): 772–81. http://dx.doi.org/10.1021/acs.bioconjchem.6b00002.

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Zhang, Shuguang. "Discovery and design of self-assembling peptides." Interface Focus 7, no. 6 (October 20, 2017): 20170028. http://dx.doi.org/10.1098/rsfs.2017.0028.

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Peptides are ubiquitous in nature and useful in many fields, from agriculture as pesticides, in medicine as antibacterial and antifungal drugs founded in the innate immune systems, to medicinal chemistry as hormones. However, the concept of peptides as materials was not recognized until 1990 when a self-assembling peptide as a repeating segment in a yeast protein was serendipitously discovered. Peptide materials are so called because they have bona fide materials property and are made from simple amino acids with well-ordered nanostructures under physiological conditions. These structures include well-ordered nanofibres, nanotubes and nanovesicles. These peptide materials have been used for: (i) three-dimensional tissue cell cultures of primary cells and stem cells, (ii) three-dimensional tissue printing, (iii) sustained releases of small molecules, growth factors, monoclonal antibody and siRNA, (iv) accelerated wound healing in reparative and regenerative medicine as well as tissue engineering, (v) used to stabilize membrane proteins including difficult G-protein coupled receptors and photosystem I for designing nanobiodevices, (vi) a few self-assembling peptides have been used in human clinical trials for accelerated wound healings in surgical uses and (vii) in human clinical trials for siRNA delivery for treatment of cancers. It is likely that these self-assembling peptides will open doors for more and more diverse uses. The field of self-assembling peptides is growing in a number of directions in areas of materials, synthetic biology, and clinical medicine and beyond.

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Dutta, Arpita, Suven Das, Purak Das, Suvendu Maity, Prasanta Ghosh, and Soumya Shankha Biswas. "Unique supramolecular assembly of a synthetic achiral α, γ-hybrid tripeptide." Zeitschrift für Kristallographie - Crystalline Materials 237, no. 1-3 (March 1, 2022): 77–81. http://dx.doi.org/10.1515/zkri-2022-0002.

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Abstract An achiral tripeptide, namely, Boc-γ-Abu-m-ABA-Aib-OMe (γ-Abu: γ−amino butyric acid; m-ABA: meta-aminobenzoic acid) was synthesized by solution phase procedure. The α, γ-hybrid peptide was designed in such a way that two dissimilar γ−amino acids, one flexible and another rigid, were positioned sidewise along with α-amino isobutyric acid (Aib) as C-terminal residue. The single crystal X-ray diffraction analysis revealed that two kinks were generated around centrally placed m-ABA. Interestingly, the peptide self-assembled via three intermolecular N–H···O and one intermolecular C–H···O hydrogen bonding interactions to supramlecular helical architecture.

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Machado, Raul, A. J. Ribeiro, J. Padrão, D. Silva, A. Nobre, J. A. Teixeira, F. J. Arias, António M. Cunha, José C. Rodríguez-Cabello, and M. Casal. "Exploiting the Sequence of Naturally Occurring Elastin: Construction, Production and Characterization of a Recombinant Thermoplastic Protein-Based Polymer." Journal of Nano Research 6 (June 2009): 133–45. http://dx.doi.org/10.4028/www.scientific.net/jnanor.6.133.

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Genetic engineering was used to produce an elastin-like polymer (ELP) with precise amino acid composition, sequence and length, resulting in the absolute control of MW and stereochemistry. A synthetic monomer DNA sequence encoding for (VPAVG)20, was used to build a library of concatemer genes with precise control on sequence and size. The higher molecular weight polymer with 220 repeats of VPAVG was biologically produced in Escherichia coli and purified by hot and cold centrifugation cycles, based on the reversible inverse temperature transition property of ELPs. The use of low cost carbon sources like lactose and glycerol for bacteria cells culture media was explored using Central Composite Design approach allowing optimization of fermentation conditions. Due to its self-assembling behaviour near 33 °C stable spherical microparticles with a size ~ 1µm were obtained, redissolving when a strong undercooling is achieved. The polymer produced showed hysteresis behaviour with thermal absorbing/releasing components depending on the salt concentration of the polymer solution.

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Das, Apurba K., Swarup Manna, Michael G. B. Drew, Sudip Malik, Arun K. Nandi, and Arindam Banerjee. "Low Molecular Weight Organogelators from Self-assembling Synthetic Tripeptides With Coded Amino Acids: Morphological, Structural, Thermodynamic and Spectroscopic Investigations." Supramolecular Chemistry 18, no. 8 (December 1, 2006): 645–55. http://dx.doi.org/10.1080/10610270601035553.

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Varlas, Spyridon, Georgia L. Maitland, and Matthew J. Derry. "Protein-, (Poly)peptide-, and Amino Acid-Based Nanostructures Prepared via Polymerization-Induced Self-Assembly." Polymers 13, no. 16 (August 5, 2021): 2603. http://dx.doi.org/10.3390/polym13162603.

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Proteins and peptides, built from precisely defined amino acid sequences, are an important class of biomolecules that play a vital role in most biological functions. Preparation of nanostructures through functionalization of natural, hydrophilic proteins/peptides with synthetic polymers or upon self-assembly of all-synthetic amphiphilic copolypept(o)ides and amino acid-containing polymers enables access to novel protein-mimicking biomaterials with superior physicochemical properties and immense biorelevant scope. In recent years, polymerization-induced self-assembly (PISA) has been established as an efficient and versatile alternative method to existing self-assembly procedures for the reproducible development of block copolymer nano-objects in situ at high concentrations and, thus, provides an ideal platform for engineering protein-inspired nanomaterials. In this review article, the different strategies employed for direct construction of protein-, (poly)peptide-, and amino acid-based nanostructures via PISA are described with particular focus on the characteristics of the developed block copolymer assemblies, as well as their utilization in various pharmaceutical and biomedical applications.

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Carter, Joshua D., and Thomas H. LaBean. "Coupling Strategies for the Synthesis of Peptide-Oligonucleotide Conjugates for Patterned Synthetic Biomineralization." Journal of Nucleic Acids 2011 (2011): 1–8. http://dx.doi.org/10.4061/2011/926595.

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This work describes preparation strategies for peptide-oligonucleotide conjugates that combine the self-assembling behavior of DNA oligonucleotides with the molecular recognition capabilities of peptides. The syntheses include a solution-phase fragment coupling reaction and a solid-phase fragment coupling strategy where the oligonucleotide has been immobilized on DEAE Sepharose. The yield of four coupling reagents is evaluated, two reagents in water, EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride) and DMTMM (4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium chloride), and two in dimethylformamide (DMF), PyBOP ((Benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate) and HBTU (O-benzotriazole-N,N,N′,N′-tetramethyluronium hexafluorophosphate), while the oligonucleotide fragment is either in solution or immobilized on DEAE. These coupling strategies rely on an unprotected 5′ amino linker on the oligonucleotide reacting with the peptide C-terminus. The peptide, selected from a combinatorial library for its gold-binding behavior, was 12 amino acids long with an N-terminus acetyl cap. Formation of the conjugates was confirmed by gel electrophoresis and mass spectrometry while molecular recognition functionality of the peptide portion was verified using atomic force microscopy. Solution-phase yields were superior to their solid-phase counterparts. EDC resulted in the highest yield for both solution-phase (95%) and solid-phase strategies (24%), while the DMF-based reagents, PyBOP and HBTU, resulted in low yields with reduced recovery. All recoverable conjugates demonstrated gold nanoparticle templating capability.

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Konda, Maruthi, Brice Kauffmann, Dnyaneshwar B. Rasale, and Apurba K. Das. "Structural and morphological diversity of self-assembled synthetic γ-amino acid containing peptides." Organic & Biomolecular Chemistry 14, no. 17 (2016): 4089–102. http://dx.doi.org/10.1039/c6ob00380j.

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Ghilan, Alina, Alexandra Croitoriu, Aurica P. Chiriac, Loredana Elena Nita, Maria Bercea, and Alina Gabriela Rusu. "Injectable Networks Based on a Hybrid Synthetic/Natural Polymer Gel and Self-Assembling Peptides Functioning as Reinforcing Fillers." Polymers 15, no. 3 (January 26, 2023): 636. http://dx.doi.org/10.3390/polym15030636.

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Double network (DN) hydrogels composed of self-assembling low-molecular-weight gelators and a hybrid polymer network are of particular interest for many emerging biomedical applications, such as tissue regeneration and drug delivery. The major benefits of these structures are their distinct mechanical properties as well as their ability to mimic the hierarchical features of the extracellular matrix. Herein, we describe a hybrid synthetic/natural polymer gel that acts as the initial network based on sodium alginate and a copolymer, namely poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5,5) undecane). The addition of amino acids and peptide-derived hydrogelators, such as Fmoc-Lys-Fmoc-OH and Fmoc-Gly-Gly-Gly-OH, to the already-made network gives rise to DNs crosslinked via non-covalent interactions. Fourier transform infrared spectroscopy (FTIR) and thermal analysis confirmed the formation of the DN and highlighted the interactions between the two component networks. Swelling studies revealed that the materials have an excellent water absorption capacity and can be classified as superabsorbent gels. The rheological properties were systematically investigated in response to different variables and showed that the prepared materials present injectability and a self-healing ability. SEM analysis revealed a morphology consisting of a highly porous and interconnected fibrous network. Finally, the biocompatibility was evaluated using the MTT assay on dermal fibroblasts, and the results indicated that the new structures are non-toxic and potentially useful for biomedical applications.

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Pompon, D., and A. Laisné. "PDNA as building blocks for membrane-guided self-assemblies." Biochemical Society Transactions 35, no. 3 (May 22, 2007): 495–97. http://dx.doi.org/10.1042/bst0350495.

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Different semi-synthetic PDNAs (protein–DNA complexes), which encompass a protein core engineered from the cytochrome b5 scaffold, an embedded tuneable redox cofactor, a synthetic linker and a large oligonucleotide, were designed, synthesized and purified to homogeneity. These building blocks can be reversibly attached to Ni-DOGS {1,2-dioleoyl-sn-glycero-3-[N(5-amino-1-carboxypentyl)iminodiacetic acid]succinyl}-doped supported membranes through a metal chelate bridge with the protein part and be polymerized in a fully controllable manner using a solid-phase synthesis strategy and a stepwise addition of suitable complementary oligonucleotides. The resulting structures could recreate a large range of regular distribution of patterned redox and absorbing centres separated by fully tuneable distances and geometry. Kinetic parameters for the self-assembly of building blocks were determined using SPRI (surface plasmon resonance imagery). Structures of resulting nano-objects were characterized using gel electrophoresis and single molecule approaches following decoration of assemblies with quantum dots.

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Corr, M., L. F. Boyd, S. R. Frankel, S. Kozlowski, E. A. Padlan, and D. H. Margulies. "Endogenous peptides of a soluble major histocompatibility complex class I molecule, H-2Lds: sequence motif, quantitative binding, and molecular modeling of the complex." Journal of Experimental Medicine 176, no. 6 (December 1, 1992): 1681–92. http://dx.doi.org/10.1084/jem.176.6.1681.

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To gain insight into the rules that govern the binding of endogenous and viral peptides to a given major histocompatibility complex (MHC) class I molecule, we characterized the amino acid sequences of a set of self peptides bound by a soluble analogue of murine H-2Ld, H-2Lds. We tested corresponding synthetic peptides quantitatively for binding in several different assays, and built three-dimensional computer models of eight peptide/H-2Lds complexes, based on the crystallographic structure of the human HLA-B27/peptide complex. Comparison of primary and tertiary structures of bound self and antigenic peptides revealed that residues 2 and 9 were not only restricted in sequence and tolerant of conservative substitutions, but were spatially constrained in the three-dimensional models. The degree of sequence variability of specific residues in MHC-restricted peptides reflected the lack of structural constraint on those amino acids. Thus, amino acid residues that define a peptide motif represent side chains required or preferred for a close fit with the MHC class I heavy chain.

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Levit, Mariia, Natalia Zashikhina, Alena Vdovchenko, Anatoliy Dobrodumov, Natalya Zakharova, Anna Kashina, Eckart Rühl, et al. "Bio-Inspired Amphiphilic Block-Copolymers Based on Synthetic Glycopolymer and Poly(Amino Acid) as Potential Drug Delivery Systems." Polymers 12, no. 1 (January 10, 2020): 183. http://dx.doi.org/10.3390/polym12010183.

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In this work, a method to prepare hybrid amphiphilic block copolymers consisting of biocompatible synthetic glycopolymer with non-degradable backbone and biodegradable poly(amino acid) (PAA) was developed. The glycopolymer, poly(2-deoxy-2-methacrylamido-D-glucose) (PMAG), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Two methods for modifying the terminal dithiobenzoate-group of PMAG was investigated to obtain the macroinitiator bearing a primary aliphatic amino group, which is required for ring-opening polymerization of N-carboxyanhydrides of hydrophobic α-amino acids. The synthesized amphiphilic block copolymers were carefully analyzed using a set of different physico-chemical methods to establish their composition and molecular weight. The developed amphiphilic copolymers tended to self-assemble in nanoparticles of different morphology that depended on the nature of the hydrophobic amino acid present in the copolymer. The hydrodynamic diameter, morphology, and cytotoxicity of polymer particles based on PMAG-b-PAA were evaluated using dynamic light scattering (DLS) and transmission electron microscopy (TEM), as well as CellTiter-Blue (CTB) assay, respectively. The redox-responsive properties of nanoparticles were evaluated in the presence of glutathione taken at different concentrations. Moreover, the encapsulation of paclitaxel into PMAG-b-PAA particles and their cytotoxicity on human lung carcinoma cells (A549) and human breast adenocarcinoma cells (MCF-7) were studied.

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Valdivia, Victoria, Chiara Paggiaro, and Inmaculada Fernández. "Synthesis and Characterization of New Biocompatible Amino Amphiphilic Compounds Derived from Oleic Acid as Nanovectors for Drug Delivery." Proceedings 41, no. 1 (November 14, 2019): 1. http://dx.doi.org/10.3390/ecsoc-23-06458.

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Amphiphilic molecules have been actively explored as promising materials in the field of bio and nanotechnology. These molecules are constituted by a polar head and a lipophilic tail and in an aqueous medium are self-assemble to form different types of macromolecular structures such as micelles, monolayer vesicles, bars, sheets and tubes. In this work, a convergent synthetic approach for the synthesis of two new amphiphilic compounds based on a versatile amino polar head, a tetraethylene glycol spacer and a lipophilic tail derived from oleic acid has been developed. Subsequently, after a self-assembly process in aqueous medium, nanostructures as micelles have been obtained and characterized. Finally, a procedure for the inclusion of the highly lipophilic drug Dexamethasone has been carried out in order to study the ability of these micelles to act as nanovectors for drug delivery.

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Platten, Michael, Peggy P. Ho, Sawsan Youssef, Paulo Fontoura, Hideki Garren, Eun Mi Hur, Rohit Gupta, et al. "Treatment of Autoimmune Neuroinflammation with a Synthetic Tryptophan Metabolite." Science 310, no. 5749 (November 3, 2005): 850–55. http://dx.doi.org/10.1126/science.1117634.

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Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased when myelin-specific T cells were stimulated with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory T helper–1 (TH1) cytokines. N-(3,4,-Dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating TH1-mediated autoimmune diseases such as MS.

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Sugawara-Narutaki, Ayae, Sawako Yasunaga, Yusuke Sugioka, Duc H. T. Le, Issei Kitamura, Jin Nakamura, and Chikara Ohtsuki. "Rheology of Dispersions of High-Aspect-Ratio Nanofibers Assembled from Elastin-Like Double-Hydrophobic Polypeptides." International Journal of Molecular Sciences 20, no. 24 (December 12, 2019): 6262. http://dx.doi.org/10.3390/ijms20246262.

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Elastin-like polypeptides (ELPs) are promising candidates for fabricating tissue-engineering scaffolds that mimic the extracellular environment of elastic tissues. We have developed a “double-hydrophobic” block ELP, GPG, inspired by non-uniform distribution of two different hydrophobic domains in natural elastin. GPG has a block sequence of (VGGVG)5-(VPGXG)25-(VGGVG)5 that self-assembles to form nanofibers in water. Functional derivatives of GPG with appended amino acid motifs can also form nanofibers, a display of the block sequence’s robust self-assembling properties. However, how the block length affects fiber formation has never been clarified. This study focuses on the synthesis and characterization of a novel ELP, GPPG, in which the central sequence (VPGVG)25 is repeated twice by a short linker sequence. The self-assembly behavior and the resultant nanostructures of GPG and GPPG were when compared through circular dichroism spectroscopy, atomic force microscopy, and transmission electron microscopy. Dynamic rheology measurements revealed that the nanofiber dispersions of both GPG and GPPG at an extremely low concentration (0.034 wt%) exhibited solid-like behavior with storage modulus G′ > loss modulus G” over wide range of angular frequencies, which was most probably due to the high aspect ratio of the nanofibers that leads to the flocculation of nanofibers in the dispersion.

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Guldner, H. H., H. J. Netter, C. Szostecki, E. Jaeger, and H. Will. "Human anti-p68 autoantibodies recognize a common epitope of U1 RNA containing small nuclear ribonucleoprotein and influenza B virus." Journal of Experimental Medicine 171, no. 3 (March 1, 1990): 819–29. http://dx.doi.org/10.1084/jem.171.3.819.

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Autoantibodies from patients with systemic rheumatic diseases were used to map antigenic sites on the 68-kD autoantigen (p68) associated with (U1)RNA-containing small nuclear ribonucleoprotein (snRNP) particles. With truncated recombinant fusion proteins and synthetic peptides, a subset of anti-p68 autoantibodies was found to recognize the amino acid sequence motif Glu-Arg-Lys-Arg-Arg (ERKRR). To investigate the possible involvement of epitopes shared by microbial antigens and host self-components in initiation of autoimmunity (molecular mimicry), a sequence data bank was screened for proteins containing an amino acid motif identical or related to ERKRR. The identical motif was found on the M1 matrix protein of influenza B viruses, and affinity-purified human anti-ERKRR autoantibodies recognized this epitope also in the viral amino acid sequence context. The common epitope recognized by human autoantibodies suggests that influenza B virus infection may play a role in initiation of the anti-p68 and anti-(U1)RNP autoimmune response.

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Chen, W., N. J. Ede, D. C. Jackson, J. McCluskey, and A. W. Purcell. "CTL recognition of an altered peptide associated with asparagine bond rearrangement. Implications for immunity and vaccine design." Journal of Immunology 157, no. 3 (August 1, 1996): 1000–1005. http://dx.doi.org/10.4049/jimmunol.157.3.1000.

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Abstract The extent to which peptides containing chemically and post-translationally modified amino acid side chains are recognized by primed CTL has not been clearly defined. We report on the CTL recognition of a MHC class I-restricted peptide containing a cyclized asparagine (succinimide) residue. This modification of the asparagine side chain is a common intermediate structure during deamidation, isomerization, and bond rearrangements of amide-containing amino acids and also occurs as a side reaction in peptide synthesis. The CTL specifically recognized the succinimide-containing peptide showing only weak cross-reactivity at high concentrations of the parent peptide containing unmodified asparagine. Similarly, CTL raised against the parent peptide did not recognize the succinimide derivative of this peptide. Naturally processed forms of these structures are likely to occur given the importance and frequency of deamidation both in vitro and in vivo. Moreover, since succinimide intermediates of deamidated peptides can occasionally be very stable, these peptides have the potential to act as altered self-Ags with significant implications for autoimmunity. In addition, unwanted and potentially hazardous specificities may be elicited when using synthetic peptides in subunit vaccines in which succinimide residues may form spontaneously during storage or chemical synthesis.

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Lu, Hua, Jing Wang, Ziyuan Song, Lichen Yin, Yanfeng Zhang, Haoyu Tang, Chunlai Tu, Yao Lin, and Jianjun Cheng. "Recent advances in amino acid N-carboxyanhydrides and synthetic polypeptides: chemistry, self-assembly and biological applications." Chem. Commun. 50, no. 2 (2014): 139–55. http://dx.doi.org/10.1039/c3cc46317f.

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Singh, V. K., H. K. Kalra, K. Yamaki, T. Abe, L. A. Donoso, and T. Shinohara. "Molecular mimicry between a uveitopathogenic site of S-antigen and viral peptides. Induction of experimental autoimmune uveitis in Lewis rats." Journal of Immunology 144, no. 4 (February 15, 1990): 1282–87. http://dx.doi.org/10.4049/jimmunol.144.4.1282.

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Abstract S-Antigen (S-Ag) is a well characterized 45,000 m.w. photoreceptor cell protein. When injected into susceptible animal species, including primates, it induces an experimental autoimmune uveitis, a predominantly T cell-mediated autoimmune disease of the retina and uveal tract of the eye, and of the pineal gland. In this study we found an amino acid sequence homology between a uveitopathogenic site of S-Ag, several viral proteins and one additional nonviral protein. An experimental autoimmune uveitis and pinealitis was induced in Lewis rats with these different synthetic peptides, corresponding to the amino sequence of hepatitis B virus DNA polymerase, gag-pol polyprotein of Baboon endogenous virus and gag-pol polyprotein of AKV murine leukemia virus and potato proteinase inhibitor IIa, which contain three or more consecutive amino acids identical to peptide M in S-Ag. Lymph node cells from rats immunized with either peptide M or the different synthetic peptides showed a significant degree of cross-reaction. Mononuclear cells from monkeys (Macaca fascicularis) immunized with peptide M also showed significant proliferation when incubated with either peptide M or synthetic peptides as measured by in vitro lymphocyte mitogenesis assay using [3H]TdR. Based on our findings we conclude that a viral infection may sensitize the mononuclear cells that can cross-react with self proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoantigenic event can take place in the absence of the infectious virus that initiated the immune response.

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Olesnicky, Natalie S., Andrew J. Brown, Yoichi Honda, Susan L. Dyos, Simon J. Dowell, and Lorna A. Casselton. "Self-Compatible B Mutants in Coprinus With Altered Pheromone-Receptor Specificities." Genetics 156, no. 3 (November 1, 2000): 1025–33. http://dx.doi.org/10.1093/genetics/156.3.1025.

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Abstract A successful mating in the mushroom Coprinus cinereus brings together a compatible complement of pheromones and G-protein-coupled receptors encoded by multiallelic genes at the B mating-type locus. Rare B gene mutations lead to constitutive activation of B-regulated development without the need for mating. Here we characterize a mutation that arose in the B6 locus and show that it generates a mutant receptor with a single amino acid substitution (R96H) at the intracellular end of transmembrane domain III. Using a heterologous yeast assay and synthetic pheromones we show that the mutation does not make the receptor constitutively active but permits it to respond inappropriately to a normally incompatible pheromone encoded within the same B6 locus. Parallel experiments carried out in Coprinus showed that a F67W substitution in this same pheromone enabled it to activate the normally incompatible wild-type receptor. Together, our experiments show that a single amino acid replacement in either pheromone or receptor can deregulate the specificity of ligand-receptor recognition and confer a self-compatible B phenotype. In addition, we use the yeast assay to demonstrate that different receptors and pheromones found at a single B locus belong to discrete subfamilies within which receptor activation cannot normally occur.

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Purcell, Anthony W., Weisan Chen, Nicholas J. Ede, Jeffrey J. Gorman, John V. Fecondo, David C. Jackson, Yuming Zhao, and James McCluskey. "Avoidance of Self-Reactivity Results in Skewed CTL Responses to Rare Components of Synthetic Immunogens." Journal of Immunology 160, no. 3 (February 1, 1998): 1085–90. http://dx.doi.org/10.4049/jimmunol.160.3.1085.

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Abstract In studying the CTL recognition of peptide determinants derived from the nuclear Ag La (SS-B), we observed significant skewing of the response toward rare components present within the immunogen. Thus, priming of naive mouse lymphocytes in vitro with a synthetic H-2Kb-binding peptide comprising human La (hLa) residues 51–58 resulted in class I-restricted cytotoxic T cells that failed to recognize naturally presented hLa 51–58 peptide. Instead, the majority of T hybrids recognized a low abundance (≤1%) contaminant present at picomolar concentrations in the original synthesis and identified as a peptide adduct containing N,4-t-butyl asparagine at position 6 of the hLa 51–58 sequence. The preferred T cell recognition of the butyl adduct was not due to increased affinity of this peptide for the H-2Kb molecule or to the antagonism of CTL recognizing the unmodified determinant. Rather, the bias in the immune response appeared to be the result of partial self-tolerance to the homologous mouse La 51–58 determinant, which differs from its human counterpart by only a single amino acid at position 1 (T→I). Accordingly, the CTL response appeared to be focused on “non-self” ligands present within the synthesis, even though they were present at very low concentrations. These observations have significant implications for the use of synthetic peptide vaccines, especially those designed to manipulate responses to self peptides such as tumor Ags in which self-tolerance may result in unexpected reactivity.

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Jang, Kwang-Suk. "Biolabeling and Binding Evaluation of Amphiphilic Nanocrystallopolymers." Journal of Nanomaterials 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/7416532.

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Surfactant-like inorganic-organic hybrid molecules named as nanocrystallopolymers were designed by conjugation of the hydrophilic synthetic poly(amino acid), poly-α,β-(N-(2-hydroxyethyl)l-aspartamide), with hydrophobic inorganic nanoparticles. In aqueous media, amphiphilic nanocrystallopolymers form self-aggregates with unique morphologies. Here, a simple biolabeling method of nanocrystallopolymers was developed. Biotin was selected as a model biomolecule. The specific binding of biotin-labeled nanocrystallopolymers to the targeted surface was evaluated with a surface plasmon resonance sensor.

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27

Konda, Maruthi, Soumitra Bhowmik, Shaikh M. Mobin, Sagar Biswas, and Apurba K. Das. "Modulating Hydrogen Bonded Self-assembled Patterns and Morphological Features by a Change in Side Chain of Third Amino Acid of Synthetic γ- Amino Acid Based Tripeptides." ChemistrySelect 1, no. 11 (July 16, 2016): 2586–93. http://dx.doi.org/10.1002/slct.201600557.

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28

Baxter, Richard. "A Macromolecular approach to peptide-based molecular recognition and catalysis." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C1588. http://dx.doi.org/10.1107/s2053273314084113.

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Synthetic peptides incorporating non-natural amino acids provide an opportunity to apply biomimetic principles in the design of both chemical scaffolds and novel pharmaceuticals. Crystallographic analysis can be of significant utility in this area just as elsewhere, but blur the line between small-molecule and macromolecular systems. I will present recent examples combining the tools of macromolecular crystallography techniques with chemical biology to elucidate structures of peptide-based binding and catalytic motifs. First, I will discuss recent structures of a beta-peptide known to spontaneously self-assemble into a octameric bundle wih a defined tertiary-fold. By introducing a non-natural amino acid at the solvent-exposed surface, a binding epitope for poly-alcohols is introduced. [1] Conversely, by modifying the hydrophobic core, the tertiary fold can be re-organized. [2] Second, I will discuss a peptide-based catalyst for the site-specific modification of saccharide units in the scaffold of the antibiotic teicoplanin. [3] While glycosylated small-molecules can be challenging structural-targets, native chemical ligation of the peptide to a macromolecular scaffold allowed for structure determination of the peptide and its binding target. Further structure-based design of more complex non-natural amino acid structures is a promising route to novel peptide-based tools and therapeutics.

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29

Zechel, Stefan, Martin Hager, Tobias Priemel, and Matthew Harrington. "Healing through Histidine: Bioinspired Pathways to Self-Healing Polymers via Imidazole–Metal Coordination." Biomimetics 4, no. 1 (February 27, 2019): 20. http://dx.doi.org/10.3390/biomimetics4010020.

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Biology offers a valuable inspiration toward the development of self-healing engineering composites and polymers. In particular, chemical level design principles extracted from proteinaceous biopolymers, especially the mussel byssus, provide inspiration for design of autonomous and intrinsic healing in synthetic polymers. The mussel byssus is an acellular tissue comprised of extremely tough protein-based fibers, produced by mussels to secure attachment on rocky surfaces. Threads exhibit self-healing response following an apparent plastic yield event, recovering initial material properties in a time-dependent fashion. Recent biochemical analysis of the structure–function relationships defining this response reveal a key role of sacrificial cross-links based on metal coordination bonds between Zn2+ ions and histidine amino acid residues. Inspired by this example, many research groups have developed self-healing polymeric materials based on histidine (imidazole)–metal chemistry. In this review, we provide a detailed overview of the current understanding of the self-healing mechanism in byssal threads, and an overview of the current state of the art in histidine- and imidazole-based synthetic polymers.

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30

Giraldo, Sandra, María E. Alea-Reyes, David Limón, Asensio González, Marta Duch, José A. Plaza, David Ramos-López, Joaquín de Lapuente, Arántzazu González-Campo, and Lluïsa Pérez-García. "π-Donor/π-Acceptor Interactions for the Encapsulation of Neurotransmitters on Functionalized Polysilicon-Based Microparticles." Pharmaceutics 12, no. 8 (August 1, 2020): 724. http://dx.doi.org/10.3390/pharmaceutics12080724.

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Bipyridinium salts, commonly known as viologens, are π-acceptor molecules that strongly interact with π-donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of π-donor compounds such as catecholamines and indolamines. In this work, the synthesis and characterization of four gemini-type amphiphilic bipyridinium salts (1·4PF6–4·4PF6), and their immobilization either non-covalently or covalently on polysilicon surfaces and microparticles have been achieved. More importantly, they act as hosts for the subsequent incorporation of π-donor neurotransmitters such as dopamine, serotonin, adrenaline or noradrenaline. Ultraviolet-visible absorption and fluorescence spectroscopies and high-performance liquid chromatography were used to detect the formation of the complex in solution. The immobilization of bipyridinium salts and neurotransmitter incorporation on polysilicon surfaces was corroborated by contact angle measurements. The reduction in the bipyridinium moiety and the subsequent release of the neurotransmitter was achieved using ascorbic acid, or Vitamin C, as a triggering agent. Quantification of neurotransmitter encapsulated and released from the microparticles was performed using high-performance liquid chromatography. The cytotoxicity and genotoxicity studies of the bipyridinium salt 1·4PF6, which was selected for the non-covalent functionalization of the microparticles, demonstrated its low toxicity in the mouse fibroblast cell line (3T3/NIH), the human liver carcinoma cell line (HepG2) and the human epithelial colorectal adenocarcinoma cell line (Caco-2).

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Lu, Hua, Jing Wang, Ziyuan Song, Lichen Yin, Yanfeng Zhang, Haoyu Tang, Chunlai Tu, Yao Lin, and Jianjun Cheng. "ChemInform Abstract: Recent Advances in Amino Acid N-Carboxyanhydrides and Synthetic Polypeptides: Chemistry, Self-Assembly and Biological Applications." ChemInform 45, no. 10 (February 21, 2014): no. http://dx.doi.org/10.1002/chin.201410256.

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Chicz, R. M., D. F. Graziano, M. Trucco, J. L. Strominger, and J. C. Gorga. "HLA-DP2: self peptide sequences and binding properties." Journal of Immunology 159, no. 10 (November 15, 1997): 4935–42. http://dx.doi.org/10.4049/jimmunol.159.10.4935.

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Abstract Although self peptides bound to HLA-DQ and, especially, HLA-DR allotypes have been described in some detail, few ligands that bind to HLA-DP have been identified. Toward this aim, naturally processed peptides were isolated from immunoaffinity-purified HLA-DP2 molecules expressed in cultured B lymphocytes. The size distribution of the peptide repertoire is generally similar to those reported for self peptides bound to HLA-DR and HLA-DQ molecules. Twelve peptides representing individual sequences including two nested sets were sequenced by mass spectrometry and/or N-terminal Edman analysis. Source proteins included MHC molecules and other integral membrane proteins as well as secretory and serum proteins. No dominant amino acid markers suggestive of particular enzymatic processing events were detected. Peptide specificity and affinity were examined in binding assays using synthetic peptides and purified HLA-DP and HLA-DR molecules. Anchor residues were tentatively assigned using alanine-substituted analogues of two self peptides. Some structural features of HLA-DP2 that may relate to peptide binding are considered.

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Lorenz, R. G., A. N. Tyler, and P. M. Allen. "T cell recognition of bovine ribonuclease. Self/non-self discrimination at the level of binding to the I-Ak molecule." Journal of Immunology 141, no. 12 (December 15, 1988): 4124–28. http://dx.doi.org/10.4049/jimmunol.141.12.4124.

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Abstract Bovine RNase A specific T-cell hybridomas were generated to study the recognition of foreign Ag by T lymphocytes. One hybrid, TS12, was shown to recognize RNase in association with I-Ak. This hybridoma required bovine RNase to be processed before recognition. The immunogenic determinant on the RNase molecule recognized by TS12 was localized to the tryptic fragment RNase(40-61). All of the stimulatory ability of this determinant was shown to be contained within the synthetic 14mer RNase(43-56). When this segment of bovine RNase was compared with the self murine sequence, only one amino acid difference was found, a substitution of a proline residue at position 50 for a serine residue. This substitution completely abolishes binding to the I-Ak molecule, as shown by both functional and direct binding assays. This finding shows that self/non-self discrimination not only occurs at the level of the T cell, but also can be caused by an inability of the self peptide to associate with a class II molecule.

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Akamatsu, Y., M. S. Cole, J. Y. Tso, and N. Tsurushita. "Construction of a human Ig combinatorial library from genomic V segments and synthetic CDR3 fragments." Journal of Immunology 151, no. 9 (November 1, 1993): 4651–59. http://dx.doi.org/10.4049/jimmunol.151.9.4651.

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Abstract A naive combinatorial Ig library was constructed from semi-synthetic V genes consisting of human genomic V segments and synthetic CDR3 fragments. VH and V kappa segments were amplified from human genomic DNA by polymerase chain reaction using V subgroup-specific primers. The amplified VH and V kappa segments were combined with synthetic oligonucleotides containing a J region and CDR3 with amino acid sequence variations, resulting in complete V genes. These V genes were cloned into a phagemid expression vector in a single-chain form fused to the carboxyl-terminus of the M13 minor coat protein III. Phagemid particles displaying the single chain hybrid proteins on their surface were screened with Con A as Ag. Several clones showing specific binding to Con A were obtained after four rounds of selection and were further analyzed for their binding properties and DNA sequences. This method provides a novel way to create a naive combinatorial library without using mRNA from B lymphocytes as template. The method should be useful to isolate human antibodies that react with self-Ag.

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35

Manolakis, Ioannis, and Usaid Azhar. "Recent Advances in Mussel-Inspired Synthetic Polymers as Marine Antifouling Coatings." Coatings 10, no. 7 (July 7, 2020): 653. http://dx.doi.org/10.3390/coatings10070653.

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Synthetic oligomers and polymers inspired by the multifunctional tethering system (byssus) of the common mussel (genus Mytilus) have emerged since the 1980s as a very active research domain within the wider bioinspired and biomimetic materials arena. The unique combination of strong underwater adhesion, robust mechanical properties and self-healing capacity has been linked to a large extent to the presence of the unusual α-amino acid derivative l-DOPA (l-3,4-dihydroxyphenylalanine) as a building block of the mussel byssus proteins. This paper provides a short overview of marine biofouling, discussing the different marine biofouling species and natural defenses against these, as well as biomimicry as a concept investigated in the marine antifouling context. A detailed discussion of the literature on the Mytilus mussel family follows, covering elements of their biology, biochemistry and the specific measures adopted by these mussels to utilise their l-DOPA-rich protein sequences (and specifically the ortho-bisphenol (catechol) moiety) in their benefit. A comprehensive account is then given of the key catechol chemistries (covalent and non-covalent/intermolecular) relevant to adhesion, cohesion and self-healing, as well as of some of the most characteristic mussel protein synthetic mimics reported over the past 30 years and the related polymer functionalisation strategies with l-DOPA/catechol. Lastly, we review some of the most recent advances in such mussel-inspired synthetic oligomers and polymers, claimed as specifically aimed or intended for use in marine antifouling coatings and/or tested against marine biofouling species.

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Wills, Peter R. "The generation of meaningful information in molecular systems." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 374, no. 2063 (March 13, 2016): 20150066. http://dx.doi.org/10.1098/rsta.2015.0066.

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The physico-chemical processes occurring inside cells are under the computational control of genetic (DNA) and epigenetic (internal structural) programming. The origin and evolution of genetic information (nucleic acid sequences) is reasonably well understood, but scant attention has been paid to the origin and evolution of the molecular biological interpreters that give phenotypic meaning to the sequence information that is quite faithfully replicated during cellular reproduction. The near universality and age of the mapping from nucleotide triplets to amino acids embedded in the functionality of the protein synthetic machinery speaks to the early development of a system of coding which is still extant in every living organism. We take the origin of genetic coding as a paradigm of the emergence of computation in natural systems, focusing on the requirement that the molecular components of an interpreter be synthesized autocatalytically. Within this context, it is seen that interpreters of increasing complexity are generated by series of transitions through stepped dynamic instabilities (non-equilibrium phase transitions). The early phylogeny of the amino acyl-tRNA synthetase enzymes is discussed in such terms, leading to the conclusion that the observed optimality of the genetic code is a natural outcome of the processes of self-organization that produced it.

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Fridkis-Hareli, Masha. "Design of Peptide Immunotherapies for MHC Class-II-Associated Autoimmune Disorders." Clinical and Developmental Immunology 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/826191.

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Autoimmune disorders, that occur when autoreactive immune cells are induced to activate their responses against self-tissues, affect one percent of the world population and represent one of the top 10 leading causes of death. The major histocompatibility complex (MHC) is a principal susceptibility locus for many human autoimmune diseases, in which self-tissue antigens providing targets for pathogenic lymphocytes are bound to HLA molecules encoded by disease-associated alleles. In spite of the attempts to design strategies for inhibition of antigen presentation targeting the MHC-peptide/TCR complex via generation of blocking antibodies, altered peptide ligands (APL), or inhibitors of costimulatory molecules, potent therapies with minimal side effects have yet to be developed. Copaxone (glatiramer acetate, GA) is a random synthetic amino acid copolymer that reduces the relapse rate by about 30% in relapsing-remitting multiple sclerosis (MS) patients. Based on the elucidated binding motifs of Copaxone and of the anchor residues of the immunogenic myelin basic protein (MBP) peptide to HLA-DR molecules, novel copolymers have been designed and proved to be more effective in suppressing MS-like disease in mice. In this report, we describe the rationale for design of second-generation synthetic random copolymers as candidate drugs for a number of MHC class-II-associated autoimmune disorders.

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38

SAL-MAN, Neta, and Yechiel SHAI. "Arginine mutations within a transmembrane domain of Tar, an Escherichia coli aspartate receptor, can drive homodimer dissociation and heterodimer association in vivo." Biochemical Journal 385, no. 1 (December 14, 2004): 29–36. http://dx.doi.org/10.1042/bj20041022.

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The interactions between the TM (transmembrane) domains of many membrane proteins are important for their proper functioning. Mutations of residues into positively charged ones within TM domains were reported to be involved in many genetic diseases, possibly because these mutations affect the self- and/or hetero-assembly of the corresponding proteins. To our knowledge, despite significant progress in understanding the role of various amino acids in TM–TM interactions in vivo, the direct effect of positively charged residues on these interactions has not been studied. To address this issue, we employed the N-terminal TM domain of the aspartate receptor (Tar-1) as a dimerization model system. We expressed within the ToxR TM assembly system several Tar-1 constructs that dimerize via polar- or non-polar amino acid motifs, and mutated these by replacement with a single arginine residue. Our results have revealed that a mutation in each of the motifs significantly reduced the ability of the TMs to dimerize. Furthermore, a Tar-1 construct that contained two arginine residues was unable to correctly integrate itself into the membrane. Nevertheless, an exogenous synthetic Tar-1 peptide containing these two arginine residues was able to inhibit in vivo the marked dimerization of a mutant Tar-1 construct that contained two glutamate residues at similar positions. This indicates that hetero-assembly of TM domains can be mediated by the interaction of two oppositely charged residues, probably by formation of ion pairs. This study broadens our knowledge regarding the effect of positively charged residues on TM–TM interactions in vivo, and provides a potential therapeutic approach to inhibit uncontrolled dimerization of TM domains caused by mutations of polar amino acids.

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Morla, A., and E. Ruoslahti. "A fibronectin self-assembly site involved in fibronectin matrix assembly: reconstruction in a synthetic peptide." Journal of Cell Biology 118, no. 2 (July 15, 1992): 421–29. http://dx.doi.org/10.1083/jcb.118.2.421.

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The active form of fibronectin is its extracellular matrix form, which allows for the attachment of cells and influences both the growth and migration of cells. The matrix form is assembled by cells; however, many cells are defective in this regard. Several regions within fibronectin have been shown to play a role in matrix assembly by cells. One such region has been localized into the first type III repeat of fibronectin (Chernousov, M. A., F. J. Fogerty, V. E. Koteliansky, and D. F. Mosher. J. Biol. Chem. 266:10851-10858). We have identified this site as a fibronectin-fibronectin binding site and reproduced it as a synthetic peptide. This site is contained in a 14-kD fragment that corresponds to portions of the first two type III repeats. The 14-kD fragment was found to bind to cell monolayers and to inhibit fibronectin matrix assembly. The 14-kD fragment only slightly reduced the binding of fibronectin to cell surfaces but it significantly inhibited the subsequent incorporation of fibronectin into the extracellular matrix. The 14-kD fragment also bound to purified fibronectin and inhibited fibronectin-fibronectin binding. A synthetic 31-amino acid peptide (P1) representing a segment of the 14-kD fragment retained the ability to inhibit fibronectin-fibronectin binding. Peptide P1 specifically bound fibronectin from plasma in affinity chromatography, whereas a column containing another peptide from the 14-kD fragment did not. These results define a fibronectin-fibronectin binding site that appears to promote matrix assembly by allowing the assembly of fibronectin molecules into nascent fibrils. The 14-kD fragment and the P1 peptide that contain this site inhibit matrix assembly by competing for the fibronectin-fibronectin binding.

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40

Rivas Marquina, Andrea, Federico Movilla, Olga Carolina Sánchez Montilva, Eva Rentschler, Luca Carrella, Pablo Albores, and Florencia Di Salvo. "Nickel(II) complexes based on L-amino-acid-derived ligands: synthesis, characterization and study of the role of the supramolecular structure in carbon dioxide capture." Acta Crystallographica Section B Structural Science, Crystal Engineering and Materials 76, no. 5 (September 3, 2020): 825–38. http://dx.doi.org/10.1107/s2052520620010008.

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The formation of the symmetrical μ3-carbonate-bridged self-assembled trinuclear NiII complex Na2{[Ni(LO)2(H2O)]3(μ3-CO3)} (LO is the carboxylate anion of a L-tyrosine derivative), involves atmospheric CO2 uptake. The asymmetric unit of the complex comprises an octahedral coordination for the NiII with two L-tyrosine-based ligands, a water molecule and one O atom of the carbonate bridge. The Ni3–μ3-CO3 core in this compound is the first reported of this kind according to the Cambridge Structural Database (CSD). The supramolecular structure is mainly sustained by hydrogen bonds developed by the phenolic functionality of the L-tyrosine moiety of one ligand and the carboxylate group of a neighbouring ligand. The crystal packing is then characterized by three interpenetrated supramolecular helices associated with a diastereoisomer of the type R-sup P, which is essential for the assembly process. Magnetic susceptibility and magnetization data support weak ferromagnetic exchange interactions within the novel Ni3–μ3-CO3 core. The NiII complex obtained under the same synthetic conditions but using the analogous ligand derived from the amino acid L-phenylalanine instead of L-tyrosine gives rise to to a mononuclear octahedral system. The results obtained for the different complexes demonstrate the role of the supramolecular structure regarding the CO2 uptake property for these NiII–amino-acid-based systems.

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41

Murphy, Jae, Sarah Vreugde, Alkis Psaltis, P. Wormald, and Alistair Jukes. "Nano-hemostats and a Pilot Study of Their Use in a Large Animal Model of Major Vessel Hemorrhage in Endoscopic Skull Base Surgery." Journal of Neurological Surgery Part B: Skull Base 38, no. 03 (December 12, 2016): 215–21. http://dx.doi.org/10.1055/s-0036-1597277.

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AbstractNano-hemostats are synthetic amino acid chains that self-assemble into a scaffold under certain conditions. These have been shown to be effective in stopping bleeding in small animal models of hemorrhage. Proposed mechanisms for their effect are that they form a mesh analogous to the fibrin plug in native hemostasis and that they may potentiate both platelet activation and the coagulation cascade. These may potentially become valuable adjuncts to endoscopic skull base surgery where there is the potential for both major vessel injury and smaller perforator injury to eloquent areas where bipolar cautery may not be suitable. We present a summary of the clinical studies to date and a small pilot study of nano-hemostat in an endoscopic sheep model of major vessel hemorrhage to determine its efficacy in stopping bleeding in this potentially catastrophic complication.

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42

Liu, Z., Y. K. Sun, Y. P. Xi, B. Hong, P. E. Harris, E. F. Reed, and N. Suciu-Foca. "Limited usage of T cell receptor V beta genes by allopeptide-specific T cells." Journal of Immunology 150, no. 8 (April 15, 1993): 3180–86. http://dx.doi.org/10.4049/jimmunol.150.8.3180.

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Abstract T cell reactivity to alloantigens results from direct and indirect recognition of allogeneic MHC molecules and/or peptides. Although direct recognition is not self-MHC restricted, indirect recognition, the result of alloantigen processing and presentation by host APC, is restricted by the self (responder) MHC molecule to which the allopeptide has bound. We have studied the MHC restriction and TCR usage in T cell alloreactivity to a synthetic peptide corresponding to amino acid residues 21-42 of the DR beta 1*0101 molecule. T cell lines were developed by in vitro immunization of T cells from three responders carrying the DR beta 1*1101 allele with this peptide. In all three responders, reactivity to peptide 21-42 was restricted by the DR11 molecule. A limited usage of V beta genes was found in these T cell lines, all of which shared the expression of V beta 13.2. Because indirect recognition of allopeptide may play an important role in chronic, antibody-mediated allograft rejection, study of the TCR gene usage may contribute to the development of specific immunosuppression therapy.

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43

Anderton, S. M., R. van der Zee, B. Prakken, A. Noordzij, and W. van Eden. "Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis." Journal of Experimental Medicine 181, no. 3 (March 1, 1995): 943–52. http://dx.doi.org/10.1084/jem.181.3.943.

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Lewis rats are susceptible to several forms of experimental arthritis-induced using heat-killed Mycobacterium tuberculosis (adjuvant arthritis, or AA), streptococcal cell walls, collagen type II, and the lipoidal amine CP20961. Prior immunization with the mycobacterial 65-kD heat shock protein (hsp65) was reported to protect against AA, and other athritis models not using M. tuberculosis, via a T cell-mediated mechanism. Hsp65 shares 48% amino acid identity with mammalian hsp60, which is expressed at elevated levels in inflamed synovia. Several studies have reported cross-reactive T cell recognition of mycobacterial hsp65 and self hsp60 in arthritic and normal individuals. We previously described nine major histocompatibility complex class II-restricted epitopes in mycobacterial hsp65 recognized by Lewis rat T cells. Of these only one, covering the 256-270 sequence, primed for cross-reactive T cell responses to the corresponding region of rat hsp60. Here we have tested each hsp65 epitope for protective activity by immunizing rats with synthetic peptides. A peptide containing the 256-270 epitope, which induced cross-reactive T cells, was the only one able to confer protection against AA. Similarly, administration of a T cell line specific for this epitope protected against AA. Preimmunization with the 256-270 epitope induced T cells that responded to heat-shocked syngeneic antigen-presenting cells, and also protected against CP20961-induced arthritis, indicating that activation of T cells, recognizing an epitope in self hsp60 can protect against arthritis induced without mycobacteria. Therefore, in contrast to the accepted concept that cross-reactive T cell recognition of foreign and self antigens might induce aggressive autoimmune disease, we propose that cross-reactivity between bacterial and self hsp60 might also be used to maintain a protective self-reactive T cell population. This discovery might have important implications for understanding T cell-mediated regulation of inflammation.

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44

Baughn, R. E., A. Jiang, R. Abraham, V. Ottmers, and D. M. Musher. "Molecular mimicry between an immunodominant amino acid motif on the 47-kDa lipoprotein of Treponema pallidum (Tpp47) and multiple repeats of analogous sequences in fibronectin." Journal of Immunology 157, no. 2 (July 15, 1996): 720–31. http://dx.doi.org/10.4049/jimmunol.157.2.720.

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Abstract Molecular mimicry, resulting from structural similarities between self-determinants on host Ags and an organism's antigenic determinants (epitopes), can incite autoimmune events in certain bacterial and viral diseases. In the course of comprehensively mapping the 47-kDa lipoprotein (Tpp47) of Treponema pallidum subsp. pallidum using an overlapping synthetic peptide strategy, we identified a major immunoreactive epitope (411PGTEYT416) that exhibited considerable motif identity with multiple repeats of analogous linear sequences found in mammalian fibronectins. To further explore the importance of this motif as a probable instigator in the induction of polyspecific cross-reactive Abs, mimetic variants were synthesized for immunologic studies. Mimetics with ala (A) replacements in each amino acid position were used to determine which residues were critical for Ab binding. Animals immunized with two mimetics (PGTEYT or PGSEYT) coupled to tetanus toxoid exhibited: 1) modified responses when challenged with viable T. pallidum; and 2) classical Arthus reactions when challenged intradermally with either motif linked to a different carrier. The cross-reactive nature of the Ab responses to both mimetics was confirmed in a variety of ELISAs using mimetics, fibronectins, and collagens. Inhibition-ELISA studies with both fibronectin and an unrelated mimetic of the RGD motif suggest that intra- and intermolecular epitope spreading occurs following mimetic immunization and involves additional self-epitopes. These observations suggest that although molecular mimicry plays a pivotal role in initially triggering the anti-fibronectin and anti-collagen responses associated with disseminated syphilis, expansion of those autoimmune responses may be due to other self-epitopes once tolerance is abrogated.

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45

Ortmann, B., S. Martin, A. von Bonin, E. Schiltz, H. Hoschützky, and H. U. Weltzien. "Synthetic peptides anchor T cell-specific TNP epitopes to MHC antigens." Journal of Immunology 148, no. 5 (March 1, 1992): 1445–50. http://dx.doi.org/10.4049/jimmunol.148.5.1445.

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Abstract Several TNP-specific, H-2Kb-restricted mouse CTL clones were identified which specifically lysed target cells in the presence of tryptic digests of TNP-modified BSA. Glutaraldehyde fixation of cells revealed that the tryptic fragments did not require further cellular processing. Chromatographic fractionation of digested TNP-BSA identified the peptide TNP-BSA222-231, containing a TNP-modified lysine at BSA position 227, as the antigenic entity. The corresponding synthetic peptide was immunologically cross-reactive with the digest. All clones reactive with TNP-BSA222-231 cross-reacted with a similar peptide from mouse serum albumin (TNP-MSA126-135), favoring the assumption that TNP-BSA222-231 represents an artificial determinant, cross-reacting with some as yet unidentified, TNP-modified, Kb-associated self-peptides. Some of our clones also cross-reacted with tryptic digests of TNP-OVA or TNP-keyhole limpet hemocyanin. We interpret these findings to indicate that 1) a significant proportion of hapten (TNP) determinants for T cells are anchored to MHC via peptides; and 2) the amino acid sequence of these peptides may only partly define the specificity of the T cell-relevant hapten epitope, implying a particularly repetitive nature of these determinants. The production of T cell-antigenic hapten-peptide conjugates will hopefully open new roads to study immune responses to environmental allergens.

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Finnegan, A., M. A. Smith, J. A. Smith, J. Berzofsky, D. H. Sachs, and R. J. Hodes. "The T cell repertoire for recognition of a phylogenetically distant protein antigen. Peptide specificity and MHC restriction of staphylococcal nuclease-specific T cell clones." Journal of Experimental Medicine 164, no. 3 (September 1, 1986): 897–910. http://dx.doi.org/10.1084/jem.164.3.897.

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Previous studies (1) have indicated that the repertoire of murine T cells specific for a potentially complex protein antigen is in fact specific for a limited number of antigenic epitopes on that antigen in association with a given Ia molecule. Since those studies generally analyzed responses to antigens that differ in only a few amino acids from homologous murine molecules, it was possible that tolerance to self proteins was responsible for the limited T cell repertoire seen in responses to closely related proteins. It was therefore of interest to determine whether T cell recognition of a structurally and phylogenetically more distant protein molecule would also show specificity for a limited number of immunodominant peptides on that molecule. A series of experiments was designed to study the antigen fine specificity and MHC restriction of T cell clones specific for the bacterially derived antigen staphylococcal nuclease (Nase). T cell clones generated in (H-2b X H-2a)F1 (B6AF1) T cells were shown to be specific for Nase and to be restricted by either Ab alpha Ab beta or Ek alpha Ek beta. The fine specificity of these clones was then analyzed using cyanogen bromide and tryptic fragments and a series of overlapping 20-amino-acid synthetic peptides corresponding to and spanning the entire sequence of the Nase molecule. Two Ab alpha Ab beta-restricted clones were highly responsive to peptide 91-110, and not to other synthetic Nase peptides. In contrast, seven Ek alpha Ek beta-restricted clones were consistently responsive to peptide 81-100 and not to 91-110 or to other Nase peptides. Certain of these Ek alpha Ek beta-restricted T cells expressed an interesting crossreactivity, in that they responded to peptide 51-70 as well as to 81-100, although the response to 51-70 was characterized by a markedly shifted dose-response curve, indicating a reduced efficiency of activation by this peptide. Analysis of the amino acid sequences of these regions indicates that this unexpected crossreaction may have a structural basis. A single Nase-specific T cell line generated from BALB/c T cells was, in contrast to any of the B6AF1 clones studied, responsive only to peptide 61-80 and not to other peptides, including 81-100 or 91-110. Collectively, these findings show that Nase-specific T cells are responsive to discrete Nase peptides. Moreover, the present findings suggest that in T cell recognition of a complex and highly foreign protein antigen, a limited number of peptide epitopes are preferentially recognized by T cells in association with a given Ia molecule.

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47

Wang, Zhong, and Michael L. Cleary. "Self-Association Contributes to E2a-Pbx1-Mediated Oncogenesis." Blood 106, no. 11 (November 16, 2005): 2611. http://dx.doi.org/10.1182/blood.v106.11.2611.2611.

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Abstract Pbx1 is a proto-oncogene that was originally discovered at the site of t(1;19) chromosomal translocations in pediatric acute B cell precursor leukemia. It codes for a TALE (three amino acid loop extension) class homeodomain transcription factor, which is a component of hetero-oligomeric protein complexes that regulate developmental gene expression. As a result of chromosomal translocations, Pbx1 is oncogenically activated by in-frame fusions with the E2a bHLH protein, which confers strong transcriptional activator properties and constitutive nuclear localization, bypassing the need for dimerization with Meinox homeodomain proteins to stabilize and import Pbx1 into the nucleus. E2a-Pbx1 oncoproteins retain an ability to bind DNA as a complex with Hox transcription factors, and co-expressed HoxA9 accelerates leukemogenesis. Using a biochemical approach, we have recently observed that E2a-Pbx1 self-associates through the Pbx moiety of the chimeric protein to form higher-order oligomers. Structure/function studies suggest that self-association is required for oncogenic activity since mutant E2a-Pbx1 proteins unable to self-associate are transformation defective in an in vitro myeloid progenitor serial replating assay. Interestingly, their oncogenic activity in this assay is rescued using synthetic oligomerization domains of FKBP. The drug AP21998, which disrupts FKBP-mediated oligomerization, blocks the proliferation of transformed myeloid progenitors and facilitates their terminal myeloid differentiation. In addition to self-association, the DNA binding homeodomain of Pbx1 is also required for transformation, but mutagenesis studies indicate that Pbx1 domains involved in cooperative DNA binding with Hox partners are dispensable. These studies suggest an alternative mechanism for leukemogenesis in which E2a-Pbx1 deregulates subordinate gene expression as an oligomeric complex that circumvents interactions with heterologous homeodomain proteins that otherwise modulate Pbx1 nuclear localization, DNA binding, and transcriptional activity.

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48

Ranganathan, Darshan, Sunita Kurur, K. P. Madhusudanan, and Isabella L. Karle. "Self-assembling urea-based peptidomimetics: A simple one-step synthesis and crystal structure of Core β-alanyl ureylene retro-bispeptides (MeOAaa[NHCONH]CH2CH2CONHAaaOMe; Aaa = amino acid A)." Tetrahedron Letters 38, no. 26 (June 1997): 4659–62. http://dx.doi.org/10.1016/s0040-4039(97)00960-x.

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49

Ghiso, J., A. Rostagno, J. E. Gardella, L. Liem, P. D. Gorevic, and B. Frangione. "A 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, -RHDS-, that promotes cell adhesion." Biochemical Journal 288, no. 3 (December 15, 1992): 1053–59. http://dx.doi.org/10.1042/bj2881053.

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Amyloid beta (A beta), the major constituent of the fibrils composing senile plaques and vascular amyloid deposits in Alzheimer's disease (AD) and related disorders, is a 39-42-residue self-aggregating degradation peptide of a larger multidomain membrane glycoprotein designated amyloid precursor protein (APP). An array of biological functions has been assigned to different APP domains, including growth regulation, neurotoxicity, inhibitory activity of serine proteinases and promotion of cell-cell and cell-matrix interactions. A beta is generated through an as-yet-unknown catabolic pathway that by-passes or inhibits the cleavage of APP within the A beta sequence. We have identified a 16 kDa intermediate APP C-terminal fragment containing A beta in leptomeningeal vessels of aged normal individuals and AD patients by means of its immunoreactivity with a panel of four different anti-(APP C-terminal) antibodies, indicating a different pathway of APP processing. Previous studies have indicated that the APP C-terminal domain is the most likely to be involved in cell-matrix interactions. A 109-amino-acid construct C109 with a sequence analogous to the C-terminal of APP (positions 587-695 of APP695), similar in length and immunoreactivity to the 16 kDa fragment, was found to promote cell adhesion. By use of synthetic peptides, this activity was initially located to the extracellular 28 residues of A beta. Inhibition studies demonstrated that the sequence RHDS (amino acids 5-8 of A beta, corresponding to residues 601-604 of APP695 was responsible for the adhesion-promoting activity. The interaction is dependent on bivalent cations and can be blocked either by the tetrapeptides RHDS and RGDS or by an anti-(beta 1 integrin) antibody. Thus, through integrin-like surface receptors, APP or its derivative proteolytic fragments containing the sequence RHDS may modulate cell-cell or cell-matrix interactions.

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Haro, Kurtis J., Marta Gomez-Nunez, Tao Dao, Deming Chau, Annie Won, Sindy Escobar-Alvarez, Victoriya Zakhaleva, Tatyana Korontsvit, David Gin, and David A. Scheinberg. "Photo-Reactive and Non-Natural Amino Acid Epitopes of Human WT1 Enhance Immunogenicity and Allow Kinetic Study of Antigen Processing." Blood 110, no. 11 (November 16, 2007): 2311. http://dx.doi.org/10.1182/blood.v110.11.2311.2311.

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Abstract Wilms tumor protein (WT1) is a transcription factor selectively over expressed in several types of leukemia and solid tumors, making it a promising potential target antigen for immunotherapy. Several open clinical trials use native or altered peptide sequences derived from the WT1 protein in order to overcome the weak immunogenicity of the self-antigen. Here we report a new strategy to circumvent tolerance by designing peptides that incorporate non-natural amino acids into the native sequence of WT1 peptides. Starting from the nonamer sequences WT1 187–195 and WT1 235–243, eight peptides containing natural amino acids and nine peptides in which different chemical modifications (fluorination, photo-reactive azido groups or benzophenone groups) were introduced at major histocompatibility complex (MHC) and T cell receptor binding positions, were synthesized. The new non-natural peptides could stabilize MHC class I molecules better than the native sequences and were also able to elicit strong specific T-cell responses. Photo-reactive peptides were additionally modified with biotin handles to allow streptavidin-biotin pull down and western blot analysis of kinetics of binding and catabolism. Upon UV irradiation, these peptides covalently bound to MHC molecules on the live cells; clearance of the peptide-MHC covalent complex occurred over 24 hours, consistent with the T2 thermo-stabilization data for the same peptide. Further catabolic studies may elucidate the important or novel cellular proteins involved in antigenic peptide processing and cross presentation and should aid in vaccine development. We are investigating whether covalent interaction with the MHC may lead to alterations in immune responses as well. T cells stimulated with one of the synthetic peptides (WT1J-W4WF) cross-reacted with the native WT1J sequence and were able to kill WT1 positive HLA-A0201 matched acute lymphoblastic leukemia cell lines. In conclusion, this study shows that peptides with non-natural amino acids can be successfully incorporated into T cell epitopes to provide increased immunogenicity and novel biological information.

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Journal articles on the topic 'Synthetic Self-assembling Amino Acid'

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