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1
Oszwałdowski, Sławomir, Katarzyna Zawistowska-Gibuła, and Kenneth Roberts. "Characterization of CdSe quantum dots with bidentate ligands by capillary electrophoresis." Open Chemistry 9, no. 4 (August 1, 2011): 572–84. http://dx.doi.org/10.2478/s11532-011-0037-3.
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AbstractThe CdSe quantum dots (QDs) with bidentate ligands: a-diimine (NN) and dihydrolipoic acid (DHLA) were synthesized and characterized by UV-Vis, particle size and capillary electrophoretic techniques. Two systems were analyzed: CdSe with one ligand (CdSe/ligand) and CdSe with two different ligands (CdSe//ligand1/ligand2), where ligand = α-diimine or DHLA. Hydrodynamic features of functionalized QDs were characterized by zone capillary electrophoretic (CZE), and particle size techniques and these methods were consistent. It was established that CZE, micellar (MEKC) and microemulsion (MEEKC) modes were suitable for separating charged CdSe QDs and that no peaks were obtained for QDs passivated with electrically neutral ligands. For CdSe QDs with neutral (NN) ligands, a preconcentration method with the use of a micellar plug was introduced for visualizing these QDs. A sharp peak representing neutral QDs was obtained within the zone of micellar plug of a non-ionic surfactant, Here, a ligand character used for CdSe modification and the type of the electrophoretic method applied were the determining factors for the QDs peak visualization. Moreover, examples of visualization of charged and neutral QDs on the same run were presented, and for this purpose, dual mechanism (separation/preconcentration) was proposed.
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Bakhtiari, Atefeh, and Javad Safaei-Ghomi. "Effects of Chiral Ligands on the Asymmetric Carbonyl-Ene Reaction." Synlett 30, no. 15 (July 23, 2019): 1738–64. http://dx.doi.org/10.1055/s-0037-1611875.
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The carbonyl-ene reaction is one of the most well-known reactions for C–C bond formation. Based on frontier molecular orbitals (FMO), carbonyl-ene reactions occur between the highest occupied molecular orbital (HOMO) of the ene compound bearing an active hydrogen atom at the allylic center and the lowest unoccupied molecular orbital (LUMO) of the electron-deficient enophile, which is a carbonyl compound. A high activation barrier enforces the concerted ene reaction rather than a Diels–Alder reaction at high temperature. Employing a catalytic system can eliminate defects in the ene reaction, and chiral catalysts promote the reaction under mild conditions to produce optically active compounds. In this account, we highlight investigations on the effects of various classes of chiral ligands on intermolecular and intramolecular carbonyl-ene reactions.1 Introduction2 Biaryl-Type Chiral Ligands3 C 1- and C 2-Symmetric Bis(oxazoline) Ligands4 Schiff Base Ligands5 N,N′-Dioxide Ligands6 Conclusions
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Murphy, Patrick B., Feng Liu, Stephen C. Cook, Nusrat Jahan, D. Gerrard Marangoni, T. Bruce Grindley, and Peng Zhang. "Structural control of Au and Au–Pd nanoparticles by selecting capping ligands with varied electronic and steric effects." Canadian Journal of Chemistry 87, no. 11 (November 2009): 1641–49. http://dx.doi.org/10.1139/v09-127.
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Weakly interacting ligands including three Gemini surfactants, didodecyldimethylammonium bromide (DDAB), and amines (RNH2, R2NH, and R3N) were used to prepare Au nanoparticles (NPs). Aqueous Au NPs capped with DDAB and Gemini surfactants showed similar sizes (3–4 nm), whereas toluene-based NPs stabilized with DDAB, amines, and their mixtures range from 2.5 to 9.3 nm. Ligand effect on Au–Pd NP structure was also studied with EXAFS. These findings were consistently accounted for by considering the ligand’s electronic/steric effects and mixed ligands coadsorption, and suggest useful ways to control NP structure by manipulating the two effects and using mixed capping ligands.
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Finkina, Ekaterina I., Daria N. Melnikova, Ivan V. Bogdanov, Natalia S. Matveevskaya, Anastasia A. Ignatova, Ilia Y. Toropygin, and Tatiana V. Ovchinnikova. "Impact of Different Lipid Ligands on the Stability and IgE-Binding Capacity of the Lentil Allergen Len c 3." Biomolecules 10, no. 12 (December 13, 2020): 1668. http://dx.doi.org/10.3390/biom10121668.
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Previously, we isolated the lentil allergen Len c 3, belonging to the class of lipid transfer proteins, cross-reacting with the major peach allergen Pru p 3 and binding lipid ligands. In this work, the allergenic capacity of Len c 3 and effects of different lipid ligands on the protein stability and IgE-binding capacity were investigated. Impacts of pH and heat treating on ligand binding with Len c 3 were also studied. It was shown that the recombinant Len c 3 (rLen c 3) IgE-binding capacity is sensitive to heating and simulating of gastroduodenal digestion. While being heated or digested, the protein showed a considerably lower capacity to bind specific IgE in sera of allergic patients. The presence of lipid ligands increased the thermostability and resistance of rLen c 3 to digestion, but the level of these effects was dependent upon the ligand’s nature. The anionic lysolipid LPPG showed the most pronounced protective effect which correlated well with experimental data on ligand binding. Thus, the Len c 3 stability and allergenic capacity can be retained in the conditions of food heat cooking and gastroduodenal digestion due to the presence of certain lipid ligands.
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Moreno, Maria João, Luís M. S. Loura, Jorge Martins, Armindo Salvador, and Adrian Velazquez-Campoy. "Analysis of the Equilibrium Distribution of Ligands in Heterogeneous Media–Approaches and Pitfalls." International Journal of Molecular Sciences 23, no. 17 (August 28, 2022): 9757. http://dx.doi.org/10.3390/ijms23179757.
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The equilibrium distribution of small molecules (ligands) between binding agents in heterogeneous media is an important property that determines their activity. Heterogeneous systems containing proteins and lipid membranes are particularly relevant due to their prevalence in biological systems, and their importance to ligand distribution, which, in turn, is crucial to ligand’s availability and biological activity. In this work, we review several approaches and formalisms for the analysis of the equilibrium distribution of ligands in the presence of proteins, lipid membranes, or both. Special attention is given to common pitfalls in the analysis, with the establishment of the validity limits for the distinct approaches. Due to its widespread use, special attention is given to the characterization of ligand binding through the analysis of Stern–Volmer plots of protein fluorescence quenching. Systems of increasing complexity are considered, from proteins with single to multiple binding sites, from ligands interacting with proteins only to biomembranes containing lipid bilayers and membrane proteins. A new formalism is proposed, in which ligand binding is treated as a partition process, while considering the saturation of protein binding sites. This formalism is particularly useful for the characterization of interaction with membrane proteins.
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Mura, Ulrike, Matthias Pfeiffer, Rupert Handgretinger, and Peter J. Lang. "Expression of Activating Natural Killer Cell Receptor Ligands in Childhood Acute Lymphoblastic Leukemia." Blood 108, no. 11 (November 16, 2006): 4478. http://dx.doi.org/10.1182/blood.v108.11.4478.4478.
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Abstract Activating and inhibitory cell surface receptors regulate natural killer (NK) cell effector functions. The extent of expression of their activating ligands on target cells probably plays a critical role in tumor immune surveillance, but the data of this expression on blasts of leukemia patients are still poor. We examined blasts of children with ALL for the activating human NKG2D ligands MICA, MICB, ULBP1, ULBP2 and ULBP3, and for the ligands of the activating human natural cytotoxic receptors (NCRs) NKp30, NKp44 and NKp46. Using ligand specific mouse monoclonal antibodies and flow cytometry, we screened 24 children (23 common-ALL, one pre-T-ALL) for the expression of NKG2D ligands and 15 children (all common-ALL) for NCR ligands. In 13 patients (all common-ALL), also the density of the NKG2D ligands was determined by quantitative flow cytometry. Considering cells positive for a particular ligand in case of a two fold increase of median fluorescence above negative control, 38 percent of the patients were positive for one or more NKG2D ligands, while only 13 percent expressed one or more NCR ligands at significant levels. ULBP1 was most frequently expressed (29 percent of patients positive), while no patients were positive for ULBP2 and NKp44 ligands. ULBP3 was positive in 17 percent of the patients, NKp30 and NKp46 ligands in 13 percent, MICA and MICB in 4 percent. The patient with pre-T-ALL was positive only for ULBP1. So ULBP1 was expressed more frequently, while the other NKG2D ligands were expressed less frequently in children than reported for adult leukemia patients before (Salih et al. Blood.2003;102:1389–1396.). The density of detected NKG2D ligand molecules was always rather low. For MICA the maximum were 1700 molecules per cell in a single patient, for MICB 900, for ULBP1 1100, and for ULBP3 1000 molecules per cell. In summary, blasts of pediatric ALL patients displayed low or negative surface levels of ligands for the human activating NK cell receptors NKG2D, NKp30, NKp44 and NKp46. QUALITATIVE LIGAND EXPRESSION QUALITATIVE LIGAND EXPRESSION QUANTITATIVE LIGAND EXPRESSION QUANTITATIVE LIGAND EXPRESSION
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Miller, Shannon M., Van Cybulski, Lois Walsh, Mark Livesay, Laura Bess, David J. Burkhart, Helene Bazin-Lee, and Jay T. Evans. "Investigation of novel TLR7/8 ligands in combination with TLR4 ligands as adjuvants to drive cell mediated anti-influenza immunity." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 125.16. http://dx.doi.org/10.4049/jimmunol.200.supp.125.16.
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Abstract Influenza is a highly communicative viral pathogen that infects 9–35 million individuals and results in 12,000–56,000 deaths in the US annually. For the most commonly used seasonal influenza vaccine, historical efficacy rates range from 10–60% thus improvements to the current vaccine are needed. We identified a novel series of synthetic TLR7/8 ligands that improve influenza vaccine efficacy when used alone or in combination with our synthetic TLR4 ligand. In human PBMCs, TLR7/8 ligands elicited secretion of the inflammatory cytokines TNFα, IL-6, and IL-1β as well as the Th1-polarizing cytokine IL12-p70. These responses can be altered by modification of novel structural features of the TLR7/8 ligands. The addition of a synthetic TLR4 ligand modified the cytokine expression profile, indicating that the structure of a TLR7/8 ligand and/or addition of a TLR4 ligand can drive substantive changes in the innate immune response. To evaluate the adjuventicity of these TLR ligands, Balb/c mice were vaccinated with split-flu vaccine containing TLR7/8 ligands alone or in combination with our TLR4 ligand. TLR7/8 ligands increased influenza-specific total IgG and IgG2a, but not IgG1, over antigen alone. Addition of a TLR4 ligand further increased influenza-specific total IgG and IgG2a. These data demonstrate that these ligands act as adjuvants to promote a Th1 skewed humoral response. The combination of TLR7/8 and TLR4 ligands elicited superior cell mediated immunity compared to either TLR7/8 or TLR4 ligand alone. These data demonstrate that heightened innate and adaptive immune responses can be elicited through a combination adjuvant using novel synthetic TLR7/8 and TLR4 ligands.
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Fan, Qikui, Hao Yang, Juan Ge, Shumeng Zhang, Zhaojun Liu, Bo Lei, Tao Cheng, Youyong Li, Yadong Yin, and Chuanbo Gao. "Customizable Ligand Exchange for Tailored Surface Property of Noble Metal Nanocrystals." Research 2020 (January 21, 2020): 1–12. http://dx.doi.org/10.34133/2020/2131806.
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It is highly desirable, while still challenging, to obtain noble metal nanocrystals with custom capping ligands, because their colloidal synthesis relies on specific capping ligands for the shape control while conventional ligand exchange processes suffer from “the strong replaces the weak” limitation, which greatly hinders their applications. Herein, we report a general and effective ligand exchange approach that can replace the native capping ligands of noble metal nanocrystals with virtually any type of ligands, producing flexibly tailored surface properties. The key is to use diethylamine with conveniently switchable binding affinity to the metal surface as an intermediate ligand. As a strong ligand, it in its original form can effectively remove the native ligands; while protonated, it loses its binding affinity and facilitates the adsorption of new ligands, especially weak ones, onto the metal surface. By this means, the irreversible order in the conventional ligand exchange processes could be overcome. The efficacy of the strategy is demonstrated by mutual exchange of the capping ligands among cetyltrimethylammonium, citrate, polyvinylpyrrolidone, and oleylamine. This novel strategy significantly expands our ability to manipulate the surface property of noble metal nanocrystals and extends their applicability to a wide range of fields, particularly biomedical applications.
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Sim, Jaeung, Taemin Kim, and Jin Kuk Yang. "Poly[(μ6-benzene-1,3,5-tricarboxylato-κ6O1:O1′:O3:O3′:O5:O5′)tris(N,N-dimethylformamide-κO)tris(μ3-formato-κ3O:O:O′)trizinc(II)]." Acta Crystallographica Section E Structure Reports Online 69, no. 11 (October 26, 2013): m619. http://dx.doi.org/10.1107/s1600536813028687.
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The asymmetric unit of the title compound, [Zn3(HCO2)3(C9H3O6)(C3H7NO)3]n, contains one Zn ion, one formate ligand, oneN,N-dimethylformamide (DMF) ligand and one-third of a benzene-1,3,5-tricarboxylate (btc) ligand situated on a crystallographic 3 axis. Each ZnIIatom is coordinated by one O atom from a DMF ligand, two O atoms from two btc ligands and three O atoms from three formate ligands in a distorted octahedral geometry. The ZnIIatoms are connected by the formate and btc ligands, forming hexanuclear cores, which are linked by btc ligands, constructing a two-dimensional layered network along theabplane.
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Crawford, Sarah M., Craig A. Wheaton, Vinayak Mishra, and Mark Stradiotto. "Probing the effect of donor-fragment substitution in Mor-DalPhos on palladium-catalyzed C–N and C–C cross-coupling reactivity." Canadian Journal of Chemistry 96, no. 6 (June 2018): 578–86. http://dx.doi.org/10.1139/cjc-2017-0749.
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The competitive catalytic screening of 18 known and newly prepared Mor-DalPhos ligand variants in the palladium-catalyzed cross-coupling of chlorobenzene with aniline, octylamine, morpholine, indole, ammonia, or acetone is presented, including ligands derived from the new secondary phosphine HP(Me2Ad)2 (Me2Ad = 3,5-dimethyladamantyl). Although triarylphosphine ancillary ligand variants performed poorly in these test reactions, ligands featuring either PAd2 or P(Me2Ad)2 donors (Ad = 1-adamantyl) gave rise to superior catalytic performance. Multiple Mor-DalPhos variants proved effective in cross-couplings involving aniline, octylamine, or morpholine; conversely, only a smaller subset of ligands proved useful in related cross-couplings of indole, ammonia, or acetone. In the case of the N-arylation of indole, a Mor-DalPhos ligand variant featuring ortho-disposed PAd2 and dimethylmorpholino donor fragments (L13) proved superior to all other ligands surveyed, including the parent ligand Mor-DalPhos (L5). Conversely, L5 was found to be superior to all other ligands in the palladium-catalyzed monoarylation of ammonia. Ligand L6 (i.e., the P(Me2Ad)2 variant of L5) proved superior to all other ligands in the monoarylation of acetone and, with the exception of indole N-arylation, was the most broadly useful of the Mor-DalPhos ligands surveyed herein.
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Karasev, Dmitry, Boris Sobolev, Alexey Lagunin, Dmitry Filimonov, and Vladimir Poroikov. "Prediction of Protein–ligand Interaction Based on Sequence Similarity and Ligand Structural Features." International Journal of Molecular Sciences 21, no. 21 (October 31, 2020): 8152. http://dx.doi.org/10.3390/ijms21218152.
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Computationally predicting the interaction of proteins and ligands presents three main directions: the search of new target proteins for ligands, the search of new ligands for targets, and predicting the interaction of new proteins and new ligands. We proposed an approach providing the fuzzy classification of protein sequences based on the ligand structural features to analyze the latter most complicated case. We tested our approach on five protein groups, which represented promised targets for drug-like ligands and differed in functional peculiarities. The training sets were built with the original procedure overcoming the data ambiguity. Our study showed the effective prediction of new targets for ligands with an average accuracy of 0.96. The prediction of new ligands for targets displayed the average accuracy 0.95; accuracy estimates were close to our previous results, comparable in accuracy to those of other methods or exceeded them. Using the fuzzy coefficients reflecting the target-to-ligand specificity, we provided predicting interactions for new proteins and new ligands; the obtained accuracy values from 0.89 to 0.99 were acceptable for such a sophisticated task. The protein kinase family case demonstrated the ability to account for subtle features of proteins and ligands required for the specificity of protein–ligand interaction.
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Mamasakhlisov, A. Ye, and Ye Sh Mamasakhlisov. "THE CONDUCTIVITY OF THE MONOLAYER OF COMPLEXES OF DNA WITH QUANTUM DOTS IN THE PRESENCE OF INTERCALATING LIGANDS." Proceedings of the YSU A: Physical and Mathematical Sciences 53, no. 3 (250) (December 16, 2019): 203–7. http://dx.doi.org/10.46991/pysu:a/2019.53.3.203.
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The noncompetitive DNA hybridization and conductivity in the presence of non-charged ligands have been investigated and the comparison is made with the ligand-free case. It has been shown that the intercalating ligands enhance the sensitivity of the DNA chips as compared with the ligand-free case at the high enough concentration of ligands.
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Southern, Craig, Jennifer M. Cook, Zaynab Neetoo-Isseljee, Debra L. Taylor, Catherine A. Kettleborough, Andy Merritt, Daniel L. Bassoni, et al. "Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein–Coupled Receptors." Journal of Biomolecular Screening 18, no. 5 (February 8, 2013): 599–609. http://dx.doi.org/10.1177/1087057113475480.
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A variety of G-protein–coupled receptor (GPCR) screening technologies have successfully partnered a number of GPCRs with their cognate ligands. GPCR-mediated β-arrestin recruitment is now recognized as a distinct intracellular signaling pathway, and ligand-receptor interactions may show a bias toward β-arrestin over classical GPCR signaling pathways. We hypothesized that the failure to identify native ligands for the remaining orphan GPCRs may be a consequence of biased β-arrestin signaling. To investigate this, we assembled 10 500 candidate ligands and screened 82 GPCRs using PathHunter β-arrestin recruitment technology. High-quality screening assays were validated by the inclusion of liganded receptors and the detection and confirmation of these established ligand-receptor pairings. We describe a candidate endogenous orphan GPCR ligand and a number of novel surrogate ligands. However, for the majority of orphan receptors studied, measurement of β-arrestin recruitment did not lead to the identification of cognate ligands from our screening sets. β-Arrestin recruitment represents a robust GPCR screening technology, and ligand-biased signaling is emerging as a therapeutically exploitable feature of GPCR biology. The identification of cognate ligands for the orphan GPCRs and the extent to which receptors may exist to preferentially signal through β-arrestin in response to their native ligand remain to be determined.
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Minucci, S., M. Leid, R. Toyama, J. P. Saint-Jeannet, V. J. Peterson, V. Horn, J. E. Ishmael, et al. "Retinoid X receptor (RXR) within the RXR-retinoic acid receptor heterodimer binds its ligand and enhances retinoid-dependent gene expression." Molecular and Cellular Biology 17, no. 2 (February 1997): 644–55. http://dx.doi.org/10.1128/mcb.17.2.644.
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Retinoic acid receptor (RAR) and retinoid X receptor (RXR) form heterodimers and regulate retinoid-mediated gene expression. We studied binding of RXR- and RAR-selective ligands to the RXR-RAR heterodimer and subsequent transcription. In limited proteolysis analyses, both RXR and RAR in the heterodimer bound their respective ligands and underwent a conformational change in the presence of a retinoic acid-responsive element. In reporter analyses, the RAR ligand (but not the RXR ligand), when added singly, activated transcription, but coaddition of the two ligands led to synergistic activation of transcription. This activation required the AF-2 domain of both RXR and RAR. Genomic footprinting analysis was performed with P19 embryonal carcinoma cells, in which transcription of the RARbeta gene is induced upon retinoid addition. Paralleling the reporter activation data, only the RAR ligand induced in vivo occupancy of the RARbeta2 promoter when added singly. However, at suboptimal concentrations of RAR ligand, coaddition of the RXR ligand increased the stability of promoter occupancy. Thus, liganded RXR and RAR both participate in transcription. Finally, when these ligands were tested for teratogenic effects on zebra fish and Xenopus embryos, we found that coadministration of the RXR and RAR ligands caused more severe abnormalities in these embryos than either ligand alone, providing biological support for the synergistic action of the two ligands.
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Wu, Jing, Shuang Li, Tete Li, Xinping Lv, Mingyou Zhang, Guoxia Zang, Chong Qi, Yong-Jun Liu, Liang Xu, and Jingtao Chen. "pDC Activation by TLR7/8 Ligand CL097 Compared to TLR7 Ligand IMQ or TLR9 Ligand CpG." Journal of Immunology Research 2019 (April 9, 2019): 1–10. http://dx.doi.org/10.1155/2019/1749803.
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Plasmacytoid dendritic cells (pDCs) express high levels of the toll-like receptors (TLRs) TLR7 and TLR9. In response to TLR7 and TLR9 ligands, pDCs are primary producers of type I interferons. Our previous study demonstrated that pDCs activated by the TLR7 ligand imiquimod (IMQ) and the TLR9 ligand CpG A can kill breast cancer cells in vitro and inhibit tumor growth in vivo. Moreover, we observed a distinctive morphological, phenotypic change in pDCs after activation by IMQ and CpG A. However, the effect of other TLR7 and TLR9 ligands on pDCs remains less understood. In this study, we treat pDCs with the TLR7 ligand IMQ, TLR7/8 ligands (CL097 and CL075), and three TLR9 ligands (different types of CpGs). The size of pDCs increased significantly after activation by TLR7, or TLR7/8 ligands. TLR7, TLR7/8, and TLR9 ligands similarly modulated cytokine release, as well as protein expression of pDC markers, costimulatory molecules, and cytotoxic molecules. Interestingly, TLR7/8 ligands, especially CL097, induced stronger responses. These results are relevant to the further study of the role and mechanism of pDC-induced antitumor effects and may aid in the development of a new strategy for future tumor immunotherapy.
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Itoh, Yasushi, Bernhard Hemmer, Roland Martin, and Ronald N. Germain. "Serial TCR Engagement and Down-Modulation by Peptide:MHC Molecule Ligands: Relationship to the Quality of Individual TCR Signaling Events." Journal of Immunology 162, no. 4 (February 15, 1999): 2073–80. http://dx.doi.org/10.4049/jimmunol.162.4.2073.
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Abstract In the present study, we examined the relationships among quantitative aspects of TCR engagement as measured by receptor down-modulation, functional responses, and biochemical signaling events using both mouse and human T cell clones. For T cells from both species, ligands that are more potent in inducing functional responses promote TCR down-modulation more efficiently than weaker ligands. At low ligand density, the number of down-modulated TCR exceeds the number of available ligands by as much as 80–100:1 in the optimal human case, confirming the previous description of serial ligand engagement of TCR (Valitutti, et al. 1995. Nature 375:148–151). A previously unappreciated relationship involving TCR down-modulation, the pattern of proximal TCR signaling, and the extent of serial engagement was revealed by analyzing different ligands for the same TCR. Functionally, more potent ligands induce a higher proportion of fully tyrosine phosphorylated ζ-chains and a greater amount of phosphorylated ZAP-70 than less potent ligands, and the number of TCR down-modulated per available ligand is higher with ligands showing this full agonist-like pattern. The large number of receptors showing partial ζ phosphorylation following exposure to weak ligands indicates that the true extent of TCR engagement and signaling, and thus the amount of sequential engagement, is underestimated by measurement of TCR down-modulation alone, which depends on full receptor activation. These data provide new insight into T cell activation by revealing a clear relationship among intrinsic ligand quality, signal amplification by serial engagement, functional T cell responses, and observable TCR clearance from the cell surface.
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Lee, Jaeseok, Youngjun Lee, Young Mee Jung, Ju Hyun Park, Hyuk Sang Yoo, and Jongmin Park. "Discovery of E3 Ligase Ligands for Target Protein Degradation." Molecules 27, no. 19 (October 2, 2022): 6515. http://dx.doi.org/10.3390/molecules27196515.
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Target protein degradation has emerged as a promising strategy for the discovery of novel therapeutics during the last decade. Proteolysis-targeting chimera (PROTAC) harnesses a cellular ubiquitin-dependent proteolysis system for the efficient degradation of a protein of interest. PROTAC consists of a target protein ligand and an E3 ligase ligand so that it enables the target protein degradation owing to the induced proximity with ubiquitin ligases. Although a great number of PROTACs has been developed so far using previously reported ligands of proteins for their degradation, E3 ligase ligands have been mostly limited to either CRBN or VHL ligands. Those PROTACs showed their limitation due to the cell type specific expression of E3 ligases and recently reported resistance toward PROTACs with CRBN ligands or VHL ligands. To overcome these hurdles, the discovery of various E3 ligase ligands has been spotlighted to improve the current PROTAC technology. This review focuses on currently reported E3 ligase ligands and their application in the development of PROTACs.
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Shen, Lu, Yu-Yang Wang, Teng-Fei He, Lu-Yi Zou, Jing-Fu Guo, and Ai-Min Ren. "A Theoretical Investigation into the Homo- and Hetero-leptic Cu(I) Phosphorescent Complexes Bearing 2,9-dimethyl-1, 10-phenanthroline and bis [2-(diphenylphosphino)phenyl]ether Ligand." Materials 15, no. 20 (October 17, 2022): 7253. http://dx.doi.org/10.3390/ma15207253.
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Cu(I) complexes have received widespread attention as a promising alternative to traditional noble-metal complexes. Herein, we systematically study the properties of Cu(I) complexes from homo- to hetero-ligands, and found the following: (1) hetero-ligands are beneficial to regulate phosphorescent efficiency; (2) when the hetero-ligands in a tetracoordinated Cu(I) complex are 1:1, the ligands coordinate along the dx2-y2 direction of Cu(I) ion, which can observably suppress structural deformation; (3) unlike the P^P ligand, the N^N ligand can enhance the participation of Cu(I) during the transition process; (4) the addition of an appropriate amount of P^P ligand can effectively raise the energy level of HOMO (highest occupied molecular orbital), enhance the proportion of LLCT (ligand–ligand charge transfer), and thereby increase the available singlet emission transition moments which can be borrowed, thus promoting the radiative decay process. As a result, this work provides a detailed understanding of the effects of different ligands in Cu(I) complexes, and provides a valuable reference and theoretical basis for regulating and designing the phosphorescent properties of Cu(I) complexes in the future.
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Wen, Yan-Mei, Tian-Jun Feng, and Li-Xin He. "Poly[[aquabis(μ3-isonicotinato-κ3O:O′:N)tris(μ2-isonicotinato-κ3O,O′:N)(nitrato-κO)bis(μ4-oxalato-κ6O1,O2:O2:O1′,O2′:O1′)dierbium(III)tetrasilver(I)] tetrahydrate]." Acta Crystallographica Section E Structure Reports Online 65, no. 6 (May 23, 2009): m676—m677. http://dx.doi.org/10.1107/s160053680901842x.
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In the title coordination polymer, {[Ag4Er2(C6H4NO2)5(C2O4)2(NO3)(H2O)]·4H2O}n, each ErIIIatom is coordinated in a bicapped trigonal–prismatic coordination geometry by three O atoms from two isonicotinate (IN) ligands, four O atoms from two oxalate ligands and one O atom from either a nitrate ion or a water molecule, both of which are half-occupied over the same site. One AgIatom has a Y-shaped geometry defined by one N atom from one IN ligand, one O atom from another IN ligand and one O atom from an oxalate ligand. The other AgIatom is coordinated by two IN ligands and one O atom from an oxalate ligand. One of the IN ligands is disordered over an inversion center and forms a bridge between two centrosymmetric AgIions. Due to the disorder, this IN ligand coordinates to the Ag atom through either the pyridyl N or the carboxylate O atoms. The IN and oxalate ligands link the Er and Ag atoms into a three-dimensional coordination framework. O—H...O and C—H...O hydrogen bonds are observed in the crystal structure.
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Blasco, Salvador, Begoña Verdejo, María Paz Clares, and Enrique García-España. "Transition Metals Meet Scorpiand-like Ligands." Crystals 13, no. 9 (September 1, 2023): 1338. http://dx.doi.org/10.3390/cryst13091338.
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Scorpiand-like ligands combine the preorganization of the donor atoms of macrocycles and the degrees of freedom of the linear ligands. We prepared the complexes of several of these ligands with transition metal ions and made a crystallographic and water solution speciation studies. The analysis of the resulting crystal structures show that the ligands have the ability to accommodate several metal ions and that the coordination geometry is mostly determined by the ligand. Ligand 6-[3,7-diazaheptyl]-3,6,9–triaza-1-(2,6)-pyridinacyclodecaphane (L3) is an hexadentate ligand that affords a family of isostructural crystals with Cu(II), Mn(II), Ni(II) and Zn(II). The attempts to obtain Co(II) crystals afforded the Co(III) structures instead. Ligand 6-[4-(2-pyridyl)-3-azabutyl]-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane (L2) is very similar to L3 and yields structures similar to it, but its behavior in solution is very different due to the different interaction with protons. Ligand 6-(2-aminoethyl)-3,6,9–triaza-1-(2,6)-pyridinacyclodecaphane (L1) is pentadentate and its complexes allow the metal to be more accessible from the solvent. A Zn(II) structure with L1 shows the species [ZnBrHL1]2+, which exists in a narrow pH range.
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Murata, Shogo, Toshiki Mushino, Hiroki Hosoi, Kodai Kuriyama, Akinori Nishikawa, Shoichi Nagakura, Kentaro Horikawa, et al. "Soluble NKG2D Ligands Are Potential Biomarkers and Sentinels of Immune-Mediated Bone Marrow Injury in Bone Marrow Failure Syndromes." Acta Haematologica 143, no. 1 (June 19, 2019): 33–39. http://dx.doi.org/10.1159/000500657.
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Immune-mediated processes are considered important in the pathogenesis of bone marrow failure syndromes (BFS). We previously reported that natural killer group 2D (NKG2D) ligands were expressed on pathological blood cells of patients with BFS and that NKG2D immunity may be involved in bone marrow failure. In addition to membranous NKG2D ligands on the cell surface, soluble NKG2D ligands can exist in plasma. We therefore examined the relationship between soluble NKG2D ligands and blood cell counts in 86 patients with BFS, including aplastic anemia, myelodysplastic syndrome with single lineage dysplasia, and paroxysmal nocturnal hemoglobinuria. Approximately half of the BFS patients were positive for soluble NKG2D ligands in the plasma by enzyme-linked immunosorbent assay, and soluble NKG2D ligand-positive BFS patients exhibited severe cytopenia regardless of membranous NKG2D ligand expression. In vitroanalyses demonstrated that soluble ULBP1, an NKG2D ligand, down-regulated NKG2D receptors on CD2-positive cells in peripheral blood. Moreover, soluble ULBP1 attenuated the cytotoxic effects of peripheral blood mononuclear cells on K562, which express membranous ULBP1. Our results suggest that soluble NKG2D ligands can be easy-to-measure biomarkers for the prediction of activity of immune-meditated bone marrow injury in BFS and that soluble NKG2D ligands suppress redundant immune-mediated bone marrow injury.
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Pratama, Mohammad Rizki Fadhil, Hadi Poerwono, and Siswandono Siswodihardjo. "Introducing a two‐dimensional graph of docking score difference vs. similarity of ligand‐receptor interactions." Indonesian Journal of Biotechnology 26, no. 1 (March 30, 2021): 54. http://dx.doi.org/10.22146/ijbiotech.62194.
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Observation of molecular docking results was generally performed by analyzing the docking score and the interacting amino acid residues separately either in tables or graphs. Sometimes it was not easy to rank the tested ligands’ docking results, especially if there were many ligands. This study aims to introduce a new way to analyze docking results with a two‐dimensional graph between the difference in docking score and the similarity of ligand‐receptor interactions. Molecular docking was performed with one reference ligand and several test ligands. The docking score difference was obtained between the test and the reference ligands as the graph’s x‐axis. Meanwhile, the y‐axis contains the similarity of ligand‐receptor interactions, obtained from the ratio of amino acid residues and the types of interactions between the test and reference ligands. Docking result analysis was more straightforward because two critical parameters were presented in one graph. This graph could be used to support the analysis of the docking results.
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Xu, Xianjin, and Xiaoqin Zou. "Dissimilar Ligands Bind in a Similar Fashion: A Guide to Ligand Binding-Mode Prediction with Application to CELPP Studies." International Journal of Molecular Sciences 22, no. 22 (November 15, 2021): 12320. http://dx.doi.org/10.3390/ijms222212320.
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The molecular similarity principle has achieved great successes in the field of drug design/discovery. Existing studies have focused on similar ligands, while the behaviors of dissimilar ligands remain unknown. In this study, we developed an intercomparison strategy in order to compare the binding modes of ligands with different molecular structures. A systematic analysis of a newly constructed protein–ligand complex structure dataset showed that ligands with similar structures tended to share a similar binding mode, which is consistent with the Molecular Similarity Principle. More importantly, the results revealed that dissimilar ligands can also bind in a similar fashion. This finding may open another avenue for drug discovery. Furthermore, a template-guiding method was introduced for predicting protein–ligand complex structures. With the use of dissimilar ligands as templates, our method significantly outperformed the traditional molecular docking methods. The newly developed template-guiding method was further applied to recent CELPP studies.
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Chakraborty, Biswarup, Ivy Ghosh, Rahul Dev Jana, and Tapan Kanti Paine. "Oxidative C–N bond cleavage of (2-pyridylmethyl)amine-based tetradentate supporting ligands in ternary cobalt(ii)–carboxylate complexes." Dalton Transactions 49, no. 11 (2020): 3463–72. http://dx.doi.org/10.1039/c9dt04438h.
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Co(ii)–carboxylate complexes of N4 ligands containing (2-pyridylmethyl)amine backbone activate O2 and exhibit oxidative C–N bond cleavage of the ligands. The coordination of carboxylate co-ligand plays important role to affect the ligand oxidation.
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Kuldeep Patel, Richa Dubey, Shaifali Soni, Jagdish Chandra Rathi, and Neerupma Dhiman. "Molecular Docking and ADME Study of Quinoline and Chalcone based Derivatives for Anti-Cancer Activity." International Journal of Research in Pharmaceutical Sciences 12, no. 3 (September 13, 2021): 2252–64. http://dx.doi.org/10.26452/ijrps.v12i3.4849.
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Cancer is a big issue that affects people all over the world. It develops as a result of uncontrolled cell growth. The interaction between developed ligands and thymine phosphorylation was investigated in this study, which was computationally optimized. The aim of this study was to examine the anticancerous activity of designed ligands in thymine phosphorylation (PDB ID: 1UOU) in order to minimize the cost and time required to develop a novel anticancer drug with minimal side effects. All the designed ligands showed mild to excellent binding with proteins. Most of the ligands exhibited better interaction compared to reference compound Tamoxifen with pdb files. Some of the designed ligands among (1-7) in qunoline derivatives and (1-5) in Chalcone derivatives showed excellent docking scores with PDB file (1UOU) of thymine phosphorylation. All the designed ligands and Zinc databases were docked with 1UOU PDB files of protein, and it was found that out of twenty-five designed ligands in Qunoline series, ligand 25 showed the best binding (docking score −8.268) with 1UOU PDB of protein thymine phosphorylation. And that out of ten designed ligands in Chalcone series, ligand K1 showed the best binding (docking score −9.433) with 1UOU PDB of protein thymine phosphorylation. Docked ligand cavity of ligand ku 25 in qunoline series and K 9 in Chalcone series showed important hydrophobic/non-polar residues such as Ile199, Ile316, Trp119, Phe168, Ile198, Cys172, Tyr188, Tyr398, Tyr435, Phe343, Tyr60, Leu328, Leu171, and showed pi-pi interaction with Tyr326. Further wet laboratory studies are continued in our laboratory to confirm and find out the efficiency and activity of target compounds.
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Micovic, Vuk, Milovan Ivanovic, and Ljiljana Dosen-Micovic. "Structural requirements for ligands of the δ-opioid receptor." Journal of the Serbian Chemical Society 74, no. 11 (2009): 1207–17. http://dx.doi.org/10.2298/jsc0911207m.
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The ?-opioid receptor is sensitive to ligand geometry. In order to assist the synthesis of new ?-selective opioid ligands, the structure elements of ?-selective opioid ligands necessary for their effective binding were investigated. The automated docking procedure with a flexible ligand was used to simulate the binding of 17 ?-selective ligands to the ?-receptor. It was found that voluminous N-alkyl groups reduce the binding potency of naltrindole derivatives by preventing the ligands from adopting the preferred conformation in the receptor. This was confirmed by enantiospecific binding of chiral compounds where only one enantiomer adopts the naltrindole-like preferred conformation in the binding pocket. Voluminous groups replacing the hydroxyl group in the 3-hydroxybenzyl fragment of naltrindole analogs reduce the binding potency due to unfavorable steric interactions with the receptor. The two diastereoisomers of the potent ?-opioid ligand SNC80 confirmed the preferred binding conformation and the major receptor-ligand interactions.
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Ferreira-Faria, Diogo, and M. Ângela Taipa. "Thermal Stabilization of Lipases Bound to Solid-Phase Triazine-Scaffolded Biomimetic Ligands: A Preliminary Assessment." Processes 12, no. 2 (February 11, 2024): 371. http://dx.doi.org/10.3390/pr12020371.
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Biomimetic ligands are synthetic compounds that mimic the structure and binding properties of natural biological ligands. The first uses of textile dyes as pseudo-affinity ligands paved the way for the rational design and de novo synthesis of low-cost, non-toxic and highly stable triazine-scaffolded affinity ligands. A novel method to assess and enhance protein stability, employing triazine-based biomimetic ligands and using cutinase from Fusarium solani pisi as a protein model, has been previously reported. This innovative approach combined the concepts of molecular modeling and solid-phase combinatorial chemistry to design, synthesize and screen biomimetic compounds able to bind cutinase through complementary affinity-like interactions while maintaining its biological functionality. The screening of a 36-member biased combinatorial library enabled the identification of promising lead ligands. The immobilization/adsorption of cutinase onto a particular lead (ligand 3′/11) led to a noteworthy enhancement in thermal stability within the temperature range of 60–80 °C. In the present study, similar triazine-based compounds, sourced from the same combinatorial library and mimicking dipeptides of diverse amino acids, were selected and studied to determine their effectiveness in binding and/or improving the thermal stability of several lipases, enzymes which are closely related in function to cutinases. Three ligands with different compositions were screened for their potential thermostabilizing effect on different lipolytic enzymes at 60 °C. An entirely distinct enzyme, invertase from Saccharomyces cerevisiae, was also assessed for binding to the same ligands and functioned as a ‘control’ for the experiments with lipases. The high binding yield of ligand 3′/11 [4-({4-chloro-6-[(2-methylbutyl)amino]-1,3,5-triazin-2-yl}amino)benzoic acid] to cutinase was confirmed, and the same ligand was tested for its ability to bind lipases from Aspergillus oryzae (AOL), Candida rugosa (CRL), Chromobacterium viscosum (CVL), Rhizomucor miehei (RML) and Rhizopus niveus (RNL). The enzymes CRL, CVL, RNL and invertase showed significant adsorption yields to ligand 3′/11—32, 29, 36 and 94%, respectively, and the thermal stability at 60 °C of free and adsorbed enzymes was studied. CVL and RNL were also stabilized by adsorption to ligand 3′/11. In the case of CRL and invertase, which bound but were not stabilized by ligand (3′/11), other ligands from the original combinatorial library were tested. Between the two alternative ligands, one was effective at stabilizing C. rugosa lipase, while none stabilized invertase.
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Gerringa, Loes J. A., Micha J. A. Rijkenberg, Charles-Edouard Thuróczy, and Leo R. M. Maas. "A critical look at the calculation of the binding characteristics and concentration of iron complexing ligands in seawater with suggested improvements." Environmental Chemistry 11, no. 2 (2014): 114. http://dx.doi.org/10.1071/en13072.
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Environmental context The low concentration of iron in the oceans limits growth of phytoplankton. Dissolved organic molecules, called ligands, naturally present in seawater, bind iron thereby increasing its solubility and, consequently, its availability for biological uptake by phytoplankton. The characteristics of these ligands are determined indirectly with various mathematical solutions; we critically evaluate the underlying method and calculations used in these determinations. Abstract The determination of the thermodynamic characteristics of organic Fe binding ligands, total ligand concentration ([Lt]) and conditional binding constant (K′), by means of titration of natural ligands with Fe in the presence of an added known competing ligand, is an indirect method. The analysis of the titration data including the determination of the sensitivity (S) and underlying model of ligand exchange is discussed and subjected to a critical evaluation of its underlying assumptions. Large datasets collected during the International Polar Year, were used to quantify the error propagation along the determination procedure. A new and easy to handle non-linear model written in R to calculate the ligand characteristics is used. The quality of the results strongly depends on the amount of titration points or Fe additions in a titration. At least four titration points per distinguished ligand group, together with a minimum of four titration points where the ligands are saturated, are necessary to obtain statistically reliable estimates of S, K′ and [Lt]. As a result estimating the individual concentration of two ligands, although perhaps present, might not always be justified.
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Fourmy, Kévin, Duc Hanh Nguyen, Odile Dechy-Cabaret, and Maryse Gouygou. "Phosphole-based ligands in catalysis." Catalysis Science & Technology 5, no. 9 (2015): 4289–323. http://dx.doi.org/10.1039/c4cy01701c.
Full textAbstract:
This review provides an overview of phosphole-based ligand families (monophospholes, multidentate hybrid phosphole ligands, diphosphole and 2,2′-biphosphole-based ligands) and their potential in metal- and organo-catalyzed reactions (asymmetric reactions included).
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Korbecki, Jan, Mateusz Bosiacki, Dariusz Chlubek, and Irena Baranowska-Bosiacka. "Bioinformatic Analysis of the CXCR2 Ligands in Cancer Processes." International Journal of Molecular Sciences 24, no. 17 (August 27, 2023): 13287. http://dx.doi.org/10.3390/ijms241713287.
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Human CXCR2 has seven ligands, i.e., CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8/IL-8—chemokines with nearly identical properties. However, no available study has compared the contribution of all CXCR2 ligands to cancer progression. That is why, in this study, we conducted a bioinformatic analysis using the GEPIA, UALCAN, and TIMER2.0 databases to investigate the role of CXCR2 ligands in 31 different types of cancer, including glioblastoma, melanoma, and colon, esophageal, gastric, kidney, liver, lung, ovarian, pancreatic, and prostate cancer. We focused on the differences in the regulation of expression (using the Tfsitescan and miRDB databases) and analyzed mutation types in CXCR2 ligand genes in cancers (using the cBioPortal). The data showed that the effect of CXCR2 ligands on prognosis depends on the type of cancer. CXCR2 ligands were associated with EMT, angiogenesis, recruiting neutrophils to the tumor microenvironment, and the count of M1 macrophages. The regulation of the expression of each CXCR2 ligand was different and, thus, each analyzed chemokine may have a different function in cancer processes. Our findings suggest that each type of cancer has a unique pattern of CXCR2 ligand involvement in cancer progression, with each ligand having a unique regulation of expression.
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James, Marisa, Madelyn R. Shevlin, Thomas B. Green, Megan M. Smart, Colin D. McMillen, and Jared A. Pienkos. "Crystal Structures of DNA Intercalating Agents Dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq), (Benzo[i]dipyrido[3,2-a:2′,3′c]phenazine (dppn), and [Ir(ppy)2(dppn)][PF6] (Where Hppy = 2-Phenylpyridine)." Inorganics 11, no. 9 (August 29, 2023): 353. http://dx.doi.org/10.3390/inorganics11090353.
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Pyrazino-phenanthroline ligands are commonly used with transition metals as DNA intercalation agents. Herein, we report the characterization of two commonly utilized pyrazino-phenanthroline ligands, dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) and (benzo[i]dipyrido[3,2-a:2′,3′c]phenazine (dppn), by single-crystal X-ray diffraction. Additionally, the characterization of [Ir(ppy)2(dppn)][PF6], where Hppy = 2-phenylpyridine, by single-crystal X-ray diffraction is described. Both the dpq and dppn ligands crystallize as chloroform solvates where the chloroform molecule occupies the equivalent binding pocket of a metal in metal complexes of these ligands. These pyrazino-phenanthrolines are largely planar, with the dppn ligand displaying a slight twist. When the dppn ligand is coordinated to iridium(III), the dppn ligand on the resulting complex displays a significant degree of bending along the longitudinal direction of the ligand. This iridium (III) complex crystallizes as a CH2Cl2 and Et2O solvate and due to the volatility of these solvents these crystals are only stable for a few seconds outside of the mother liquor. The structures of the free ligands and the [Ir(ppy)2(dppn)][PF6] complex all display extensive π stacking interactions.
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Ben-Shlomo, Izhar, Rami Rauch, Orna Avsian-Kretchmer, and Aaron J. W. Hsueh. "Matching Receptome Genes with Their Ligands for Surveying Paracrine/Autocrine Signaling Systems." Molecular Endocrinology 21, no. 8 (August 1, 2007): 2009–14. http://dx.doi.org/10.1210/me.2007-0087.
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Abstract Sequencing of genomes from diverse organisms facilitates studies on the repertoire of genes involved in intercellular signaling. Extending previous efforts to annotate most human plasma membrane receptors in the Human Plasma Membrane Receptome database, we matched cognate ligands with individual receptors by surveying the published literature. In the updated online database we called “liganded receptome,” users can search for individual ligands or receptors to reveal their pairing partners and browse through receptor or ligand families to identify relationships between ligands and receptors in their respective families. Because local signaling systems are prevalent in diverse normal and diseased tissues, we used the liganded receptome knowledgebase to interrogate DNA microarray datasets for genome-wide analyses of potential paracrine/autocrine signaling systems. In addition to viewing ligand-receptor coexpression based on precomputed DNA microarray data, users can submit their own microarray data to perform online genome-wide searches for putative paracrine/autocrine signaling systems. Investigation of transcriptome data based on liganded receptome allows the discovery of paracrine/autocrine signaling for known ligand-receptor pairs in previously uncharacterized tissues or developmental stages. The present annotation of ligand-receptor pairs also identifies orphan receptors and ligands without known interacting partners in select families. Because hormonal ligands within the same family usually interact with paralogous receptors, this genomic approach could also facilitate matching of orphan receptors and ligands. The liganded receptome is accessible at http://receptome.stanford.edu.
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Mehta, Simpi, and Seema R. Pathak. "INSILICO DRUG DESIGN AND MOLECULAR DOCKING STUDIES OF NOVEL COUMARIN DERIVATIVES AS ANTI-CANCER AGENTS." Asian Journal of Pharmaceutical and Clinical Research 10, no. 4 (April 1, 2017): 335. http://dx.doi.org/10.22159/ajpcr.2017.v10i4.16826.
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Objective: Cancer is the major worldwide problem. It arises due to uncontrolled growth of cells. In the present study a series of novel coumarin derivatives were designed and computationallyoptimized to investigate the interaction between designed ligands and 10 pdb files of five selected proteins. The objective here was to analyse in silico anticancerous activity of designed ligands to reduce cost and time for getting novel anticancerous drug with minimum side effects.Methods: Docking studies were performed to find outmaximum interaction between designed ligands and selected five proteins using Schrondinger software Maestro. Capecitabin has been used as reference compound. Structures of selected proteins were downloaded from protein data bank.Results: All the designed ligands showed mild to excellent binding with proteins.Most of the ligands exhibited better interaction compared to reference compoundcapacitabin with all pdb files. Some of designed ligands amongst (1-7) showed excellent docking score with all pdb files(2v5z, 2v60, 2v61) ofAmine oxidase. Conclusion: All the designed ligands were docked with ten pdb files of five different proteins and it was found that out of seven designed ligand, ligand 4 showed best binding (docking score -10.139 ) with pdb 2v5z of protein Amine oxidase. Docked ligand cavity of ligand 4 showed important hydrophobic/non polar residues such asIle199,Ile316,Trp119,Phe168,Ile198,Cys172,Tyr188,Tyr398,Tyr435,Phe343,Tyr60,Leu328,Leu171 and showed pi-pi interaction with Tyr326.Further wet lab studies are continued in our laboratory to confirm and find out efficiency and activity of target compounds.Keywords: Docking, Mono Amine Oxidase, Coumarin derivatives, Anticancerous activity, binding energy, Ramachandran Plot, Hydrophobic residue.
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Park, Jumi, Taehee Kim, and Dongho Kim. "Charge Injection and Energy Transfer of Surface-Engineered InP/ZnSe/ZnS Quantum Dots." Nanomaterials 13, no. 7 (March 24, 2023): 1159. http://dx.doi.org/10.3390/nano13071159.
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Surface passivation is a critical aspect of preventing surface oxidation and improving the emission properties of nanocrystal quantum dots (QDs). Recent studies have demonstrated the critical role of surface ligands in determining the performance of QD-based light-emitting diodes (QD-LEDs). Herein, the underlying mechanism by which the capping ligands of InP/ZnSe/ZnS QDs influence the brightness and lifetime of the QD-LEDs is investigated. The electrochemical results demonstrate that highly luminescent InP/ZnSe/ZnS QDs exhibit modulated charge injection depending on the length of the surface ligand chains: short alkyl chains on the ligands are favorable for charge transport to the QDs. In addition, the correlation between the spectroscopic and XRD analyses suggests that the length of the ligand chain tunes the ligand–ligand coupling strength, thereby controlling the inter-QD energy transfer dynamics. The present findings shed new light on the crucial role of surface ligands for InP/ZnSe/ZnS QD-LED applications.
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Galstyan, Anzhela, Wei-Zheng Shen, and Bernhard Lippert. "AquaGroupAcidity in Complexes of theType trans-[Pt(NH3 )2(L)(H2O)]2+ (with L = Substituted Pyridines). Linear, yetWeak Dependence of pKa of the Aqua Ligand from L Basicity." Zeitschrift für Naturforschung B 64, no. 11-12 (December 1, 2009): 1653–61. http://dx.doi.org/10.1515/znb-2009-11-1252.
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The pKa of the aqua ligand in complexes of the type trans-[Pt(NH3)2(L)(H2O)]n+ depends on the nature of the ligand trans to H2O, as expected. With L = NH3 or NH2R and n = 2, the pKa is around 6.0 - 6.4.With L = N-heterocyclic ligands generally higher acidities of the aqua ligands are observed, with pKa values being in the range of 4.7 - 5.4. These values are between those for L = H2O, n = 2 (4.4) and L = Cl−, n = 1 (5.7). For differently substituted pyridine ligands L a linear relationship exists between the pKa of the H2O ligand and the basicity of the heterocyclic ligand L, which is relatively weak, however
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Ardiningsih, Indah, Kyyas Seyitmuhammedov, Sylvia G. Sander, Claudine H. Stirling, Gert-Jan Reichart, Kevin R. Arrigo, Loes J. A. Gerringa, and Rob Middag. "Fe-binding organic ligands in coastal and frontal regions of the western Antarctic Peninsula." Biogeosciences 18, no. 15 (August 11, 2021): 4587–601. http://dx.doi.org/10.5194/bg-18-4587-2021.
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Abstract. Organic ligands are a key factor determining the availability of dissolved iron (DFe) in the high-nutrient low-chlorophyll (HNLC) areas of the Southern Ocean. In this study, organic speciation of Fe is investigated along a natural gradient of the western Antarctic Peninsula, from an ice-covered shelf to the open ocean. An electrochemical approach, competitive ligand exchange – adsorptive cathodic stripping voltammetry (CLE-AdCSV), was applied. Our results indicated that organic ligands in the surface water on the shelf are associated with ice-algal exudates, possibly combined with melting of sea ice. Organic ligands in the deeper shelf water are supplied via the resuspension of slope or shelf sediments. Further offshore, organic ligands are most likely related to the development of phytoplankton blooms in open ocean waters. On the shelf, total ligand concentrations ([Lt]) were between 1.2 and 6.4 nM eq. Fe. The organic ligands offshore ranged between 1.0 and 3.0 nM eq. Fe. The southern boundary of the Antarctic Circumpolar Current (SB ACC) separated the organic ligands on the shelf from bloom-associated ligands offshore. Overall, organic ligand concentrations always exceeded DFe concentrations (excess ligand concentration, [L′] = 0.8–5.0 nM eq. Fe). The [L′] made up to 80 % of [Lt], suggesting that any additional Fe input can be stabilized in the dissolved form via organic complexation. The denser modified Circumpolar Deep Water (mCDW) on the shelf showed the highest complexation capacity of Fe (αFe'L; the product of [L′] and conditional binding strength of ligands, KFe'Lcond). Since Fe is also supplied by shelf sediments and glacial discharge, the high complexation capacity over the shelf can keep Fe dissolved and available for local primary productivity later in the season upon sea-ice melting.
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Jones, W. M., G. M. Watts, M. K. Robinson, D. Vestweber, and M. A. Jutila. "Comparison of E-selectin-binding glycoprotein ligands on human lymphocytes, neutrophils, and bovine gamma delta T cells." Journal of Immunology 159, no. 7 (October 1, 1997): 3574–83. http://dx.doi.org/10.4049/jimmunol.159.7.3574.
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Abstract We compared E-selectin-binding cell surface ligands on bovine gamma delta T cells and human leukocytes using an E-selectin/Ig chimera. The chimera worked well in flow cytometric studies and showed that bovine gamma delta T cells were the only lymphocyte population in newborn animals that bound E-selectin chimera. Furthermore, the chimera blocked gamma delta T cell rolling on E-selectin. Chimera reacted with four potential glycoprotein ligands of 180, 200, 250, and 300 kDa in Western blot analysis of gamma delta T cell detergent lysates, and it specifically precipitated at least two of these E-selectin ligands (200 and 250 kDa) from lysates of cell surface biotinylated gamma delta T cells. Preclearing bovine gamma delta lysates of GD3.5 Ag and workshop cluster 1 did not abrogate E-selectin ligand precipitation, suggesting that these surface markers do not represent E-selectin ligands. Human neutrophils possessed three E-selectin-binding ligands of approximately 80 to 90, 130, and 230 kDa, while human lymphocytes variably possessed three ligands of 120, approximately 220 to 240, and 260 kDa. Cross-precipitation experiments confirmed the results of others that neutrophil L-selectin serves as the 80 to 90-kDa E-selectin ligand. The human lymphocyte approximately 220 to 240-kDa and 260-kDa ligands may be analogous to the bovine gamma delta T cell molecules, whereas the 120-kDa is unique to human cells. The identities of the human and bovine lymphocyte E-selectin ligands are unknown. Finally, E-selectin ligand-1 apparently may have a minimal role, if any, in lymphocyte/E-selectin interactions, since a polyclonal anti-E-selectin ligand-1 serum stained a minimal number of cutaneous lymphocyte-associated Ag-positive human lymphocytes and bovine gamma delta T cells.
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Leng, Qixin, Martin C. Woodle, and A. James Mixson. "Targeted Delivery of siRNA Therapeutics to Malignant Tumors." Journal of Drug Delivery 2017 (November 9, 2017): 1–22. http://dx.doi.org/10.1155/2017/6971297.
Full textAbstract:
Over the past 20 years, a diverse group of ligands targeting surface biomarkers or receptors has been identified with several investigated to target siRNA to tumors. Many approaches to developing tumor-homing peptides, RNA and DNA aptamers, and single-chain variable fragment antibodies by using phage display, in vitro evolution, and recombinant antibody methods could not have been imagined by researchers in the 1980s. Despite these many scientific advances, there is no reason to expect that the ligand field will not continue to evolve. From development of ligands based on novel or existing biomarkers to linking ligands to drugs and gene and antisense delivery systems, several fields have coalesced to facilitate ligand-directed siRNA therapeutics. In this review, we discuss the major categories of ligand-targeted siRNA therapeutics for tumors, as well as the different strategies to identify new ligands.
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Ciccarelli, Emma Jo, Zachary Wing, Moshe Bendelstein, Ramandeep Kaur Johal, Gurjot Singh, Ayelet Monas, and Cathy Savage-Dunn. "TGF-β ligand cross-subfamily interactions in the response of Caenorhabditis elegans to a bacterial pathogen." PLOS Genetics 20, no. 6 (June 14, 2024): e1011324. http://dx.doi.org/10.1371/journal.pgen.1011324.
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The Transforming Growth Factor beta (TGF-β) family consists of numerous secreted peptide growth factors that play significant roles in cell function, tissue patterning, and organismal homeostasis, including wound repair and immunity. Typically studied as homodimers, these ligands have the potential to diversify their functions through ligand interactions that may enhance, repress, or generate novel functions. In the nematode Caenorhabditis elegans, there are only five TGF-β ligands, providing an opportunity to dissect ligand interactions in fewer combinations than in vertebrates. As in vertebrates, these ligands can be divided into bone morphogenetic protein (BMP) and TGF-β/Activin subfamilies that predominantly signal through discrete signaling pathways. The BMP subfamily ligand DBL-1 has been well studied for its role in the innate immune response in C. elegans. Here we show that all five TGF-β ligands play a role in survival on bacterial pathogens. We also demonstrate that multiple TGF-β ligand pairs act nonredundantly as part of this response. We show that the two BMP-like ligands–DBL-1 and TIG-2 –function independently of each other in the immune response, while TIG2/BMP and the TGF-β/Activin-like ligand TIG-3 function together. Structural modeling supports the potential for TIG-2 and TIG-3 to form heterodimers. Additionally, we identify TIG-2 and TIG-3 as members of a rare subset of TGF-β ligands lacking the conserved cysteine responsible for disulfide linking mature dimers. Finally, we show that canonical DBL1/BMP receptor and Smad signal transducers function in the response to bacterial pathogens, while components of the DAF7 TGF-β/Activin signaling pathway do not play a major role in survival. These results demonstrate a novel potential for BMP and TGF-β/Activin subfamily ligands to interact and may provide a mechanism for distinguishing the developmental and homeostatic functions of these ligands from an acute response such as the innate immune response to bacterial pathogens.
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Balakrishnan, M., P. Supriya, S. K. Soam, Rao CH Srinivasa, and K. Sumalatha. "Comparative Molecular docking analysis of Target fruit ripening enzyme Tomato Beta galactosidase (TBG-4)." Research Journal of Biotechnology 17, no. 1 (December 25, 2021): 29–39. http://dx.doi.org/10.25303/1701rjbt2939.
Full textAbstract:
Tomatoes comprise a high level of TBG4 (Tomato Beta galactosidase-4) enzyme activity that plays a key role in fruit softening by significant changes in the galactosyl content in the pericarp cell wall. In the present work, in silico docking studies of beta galactosidase with specific elucidated ligands were carried out. For the better understanding of protein ligand interactions, a set of 16 ligands were used for docking studies. In the present study, two different comparative docking softwares, Autodock4.0 and iGEMDOCK were used to study the protein–ligand interactions and performed to get the best docking scores. PLIP software was used for visualization of protein ligand complex and their interactions. Binding energies of 16 ligands were predicted among which 5 ligands 151, 2FL, B2G, EPE and LAT were analysed and confirmed as best ligands. Among them 151(2S)-3-Methyl-2-((2R,3S)-3- [(Mehtylsulfonyl)amino]-1-[2-(Pyrolidin-1-ylmethyl)- 1,3-Oxazol-4yl} Butanoic acid is the best inhibitor of TBG4 enzyme activity leading to significant enhancement in fruit shelf life.
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Ben-Shlomo, Izhar, and Aaron J. W. Hsueh. "Three’s Company: Two or More Unrelated Receptors Pair with the Same Ligand." Molecular Endocrinology 19, no. 5 (May 1, 2005): 1097–109. http://dx.doi.org/10.1210/me.2004-0451.
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Abstract Intercellular communication relies on signal transduction mediated by extracellular ligands and their receptors. Although the ligand-receptor interaction is usually a two-player event, there are selective examples of one polypeptide ligand interacting with more than one phylogenetically unrelated receptor. Likewise, a few receptors interact with more than one polypeptide ligand, and sometimes with more than one coreceptor, likely through an interlocking of unique protein domains. Phylogenetic analyses suggest that for certain triumvirates, the matching events could have taken place at different evolutionary times. In contrast to a few polypeptide ligands interacting with more than one receptor, we found that many small nonpeptide ligands have been paired with two or more plasma membrane receptors, nuclear receptors, or channels. The observation that many small ligands are paired with more than one receptor type highlights the utilitarian use of a limited number of cellular components during metazoan evolution. These conserved ligands are ubiquitous cell metabolites likely favored by natural selection to establish novel regulatory networks. They likely possess structural features useful for designing agonistic and antagonistic drugs to target diverse receptors.
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Horiuchi, Keisuke, Sylvain Le Gall, Marc Schulte, Takafumi Yamaguchi, Karina Reiss, Gillian Murphy, Yoshiaki Toyama, Dieter Hartmann, Paul Saftig, and Carl P. Blobel. "Substrate Selectivity of Epidermal Growth Factor-Receptor Ligand Sheddases and their Regulation by Phorbol Esters and Calcium Influx." Molecular Biology of the Cell 18, no. 1 (January 2007): 176–88. http://dx.doi.org/10.1091/mbc.e06-01-0014.
Full textAbstract:
Signaling via the epidermal growth factor receptor (EGFR), which has critical roles in development and diseases such as cancer, is regulated by proteolytic shedding of its membrane-tethered ligands. Sheddases for EGFR-ligands are therefore key signaling switches in the EGFR pathway. Here, we determined which ADAMs (a disintegrin and metalloprotease) can shed various EGFR-ligands, and we analyzed the regulation of EGFR-ligand shedding by two commonly used stimuli, phorbol esters and calcium influx. Phorbol esters predominantly activate ADAM17, thereby triggering a burst of shedding of EGFR-ligands from a late secretory pathway compartment. Calcium influx stimulates ADAM10, requiring its cytoplasmic domain. However, calcium influx-stimulated shedding of transforming growth factor α and amphiregulin does not require ADAM17, even though ADAM17 is essential for phorbol ester-stimulated shedding of these EGFR-ligands. This study provides new insight into the machinery responsible for EGFR-ligand release and thus EGFR signaling and demonstrates that dysregulated EGFR-ligand shedding may be caused by increased expression of constitutively active sheddases or activation of different sheddases by distinct stimuli.
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Solo, Peter, Sangdintuile Zeliang, Muluvelu Lohe, Avünü Neikha, and Akumsunep Jamir. "Structure-based Drug Design, ADME and Molecular Docking analyses of anti-viral agents against SARS-CoV-2 virus, Zika virus and Hepatitis C virus." Journal of Drug Delivery and Therapeutics 13, no. 7 (July 15, 2023): 65–74. http://dx.doi.org/10.22270/jddt.v13i7.5909.
Full textAbstract:
Computer-aided drug design has been taking an increasing role in the field of modern drug discovery. These in silico computational methods are cost-effective, reduce the use of animal models in pharmacological research, and can be used to study pathogenic organisms without the need for any facilities. Based on the structure of known anti-viral agents, a total of 812 ligands have been designed. All ligands were screened for drug-likeness based on Lipinski rule of five. A database of ligands was constructed and in silico docking analyses were performed using MOE 2015.10 program against three selected viruses, viz., Zika virus, Hepatitis C virus and SARS-CoV-2 virus. Ligand 93 (-8.4469 kcal/mol) and ligand 123 (-8.3609 kcal/mol) were identified to be having higher docking scores as compared to the native ligand 6T8 (-8.2839 kcal/mol) and could be considered potential candidates for further studies in anti-viral drugs against Zika virus. Ligands 153 (-10.3108 kcal/mol), 63 (-9.9968 kcal/mol), 621 (-9.8700 kcal/mol), 31 (-9.5001 kcal/mol) and 779 (-9.3874 kcal/com) were identified as the top five binding ligands, and have docking scores much higher than the reference native ligand K4J (-8.9037 kcal/com). All these ligands can be potent candidates for anti-viral research against Hepatitis C virus. Ligand 798 (-8.0957 kcal/com) and ligand 63 (-8.0778 kcal/com) have higher docking scores as compared to the reference native ligand X77 (-8.0689 kcal/mol), they also interact with the catalytic dyad at the active site of the target protein and can be considered as possible candidates for studies in anti-viral drugs against SARS-CoV-2.
Keywords: Computer-aided drug design, ADME, Molecular Docking analyses, anti-viral agents, Sars-CoV-2 virus, Zika virus, Hepatitis C virus
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Stefansson, S., M. Z. Kounnas, J. Henkin, R. K. Mallampalli, D. A. Chappell, D. K. Strickland, and W. S. Argraves. "gp330 on type II pneumocytes mediates endocytosis leading to degradation of pro-urokinase, plasminogen activator inhibitor-1 and urokinase-plasminogen activator inhibitor-1 complex." Journal of Cell Science 108, no. 6 (June 1, 1995): 2361–68. http://dx.doi.org/10.1242/jcs.108.6.2361.
Full textAbstract:
Glycoprotein 330 (gp330) is a member of a family of receptors related to the low density lipoprotein receptor (LDLR). Although several ligands have been shown to bind gp330 in solid-phase assays, the ability of gp330 to mediate ligand endocytosis has not been demonstrated. To develop a cellular model for gp330 function we screened a variety of cultured cell lines and identified several that expressed this protein, including immortalized rat type II pneumocytes and a human and two rodent tumor cell lines. Using type II pneumocytes, endocytosis of a previously described gp330 ligand, urokinase (uPA) complexed with plasminogen activator inhibitor-1 (uPA:PAI-1) and two new ligands, PAI-1 and pro-uPA, was demonstrated. RAP, the 39 kDa receptor-associated protein known to antagonize ligand binding to gp330 in solid-phase binding assays, completely inhibited both internalization and degradation of the radiolabeled ligands by type II pneumocytes. This suggested that the clearance of these ligands was dependent on either gp330 or the LDLR-related protein (LRP), which shares several ligand-binding characteristics with gp330. By using polyclonal antibodies to gp330, the cellular internalization and degradation of the ligands were inhibited by 30–50%; remaining ligand internalization and degradation activity could be partially inhibited by polyclonal antibodies against LRP. These findings indicate that gp330, like other LDLR family members, mediates endocytosis of its ligands. In addition, gp330 acts in concert with LRP in type II pneumocytes to mediate clearance of a variety of proteins involved in plasminogen activation, including uPA:PAI-1 complexes PAI-1 and pro-uPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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Urien, S., F. Brée, B. Testa, and J. P. Tillement. "pH-dependency of basic ligand binding to α1-acid glycoprotein (orosomucoid)." Biochemical Journal 280, no. 1 (November 15, 1991): 277–80. http://dx.doi.org/10.1042/bj2800277.
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The binding interactions of a series of basic ligands with alpha 1-acid glycoprotein (AAG) were examined as a function of pH. The binding to AAG increased with increasing pH, and the binding data were satisfactorily fitted to a model that incorporates the effect of pH and discriminates the association constants of neutral (non-protonated) and protonated forms of ligands. It was shown that ligands in the neutral form have a markedly higher affinity for AAG than the protonated forms, resulting in a concomitant decrease in the pKa of bound ligands. The u.v.-visible difference spectra generated upon binding of a representative ligand to AAG also showed that there was a contribution to the binding arising from the deprotonation of the ligand. It is suggested that all tested ligands bind similarly to AAG and that hydrophobic interactions dominate high-affinity binding to AAG.
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Ruff, Kiersten M., Furqan Dar, and Rohit V. Pappu. "Ligand effects on phase separation of multivalent macromolecules." Proceedings of the National Academy of Sciences 118, no. 10 (March 2, 2021): e2017184118. http://dx.doi.org/10.1073/pnas.2017184118.
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Biomolecular condensates enable spatial and temporal control over cellular processes by concentrating biomolecules into nonstoichiometric assemblies. Many condensates form via reversible phase transitions of condensate-specific multivalent macromolecules known as scaffolds. Phase transitions of scaffolds can be regulated by changing the concentrations of ligands, which are defined as nonscaffold molecules that bind to specific sites on scaffolds. Here, we use theory and computation to uncover rules that underlie ligand-mediated control over scaffold phase behavior. We use the stickers-and-spacers model wherein reversible noncovalent cross-links among stickers drive phase transitions of scaffolds, and spacers modulate the driving forces for phase transitions. We find that the modulatory effects of ligands are governed by the valence of ligands, whether they bind directly to stickers versus spacers, and the relative affinities of ligand–scaffold versus scaffold–scaffold interactions. In general, all ligands have a diluting effect on the concentration of scaffolds within condensates. Whereas monovalent ligands destabilize condensates, multivalent ligands can stabilize condensates by binding directly to spacers or destabilize condensates by binding directly to stickers. Bipartite ligands that bind to stickers and spacers can alter the structural organization of scaffold molecules within condensates even when they have a null effect on condensate stability. Our work highlights the importance of measuring dilute phase concentrations of scaffolds as a function of ligand concentration in cells. This can reveal whether ligands modulate scaffold phase behavior by enabling or suppressing phase separation at endogenous levels, thereby regulating the formation and dissolution of condensates in vivo.
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Perumal, Suguna, Raji Atchudan, Eckart Rühl, and Christina Graf. "Controlled Synthesis of Platinum and Silver Nanoparticles Using Multivalent Ligands." Nanomaterials 12, no. 13 (July 4, 2022): 2294. http://dx.doi.org/10.3390/nano12132294.
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Here, the controlled formation of platinum nanoparticles (PtNPs) and silver nanoparticles (AgNPs) using amine-functionalized multivalent ligands are reported. The effects of reaction temperature and ligand multivalency on the growth kinetics, size, and shape of PtNPs and AgNPs were systematically studied by performing a stepwise and a one-step process. PtNPs and AgNPs were prepared in the presence of amine ligands using platinum (II) acetylacetonate and silver (I) acetylacetonate, respectively. The effects of ligands and temperature on the formation of PtNPs were studied using a transmission electron microscope (TEM). For the characterization of AgNPs, additionally, ultraviolet-visible (UV-Vis) absorption was employed. The TEM measurements revealed that PtNPs prepared at different temperatures (160–200 °C, in a stepwise process) are monodispersed and of spherical shape regardless of the ligand multivalency or reaction temperature. In the preparation of PtNPs by the one-step process, ligands affect the shape of the PtNPs, which can be explained by the affinity of the ligands. The TEM and UV-Vis absorption studies on the formation of AgNPs with mono-, di-, and trivalent ligands showed narrower size distributions, while increasing the temperature from 80 °C to 120 °C and with a trivalent ligand in a one-step process.
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Lin, Hong, Hong Su, and Yun-long Feng. "catena-Poly[[diaquabis[(4-tolylsulfanyl)acetato-κO]nickel(II)]-μ-4,4′-bipyridine-κ2 N:N′]." Acta Crystallographica Section E Structure Reports Online 62, no. 4 (March 10, 2006): m747—m749. http://dx.doi.org/10.1107/s1600536806007926.
Full textAbstract:
The title complex, [Ni(C9H9O2S)2(C8H8N2)(H2O)2] n , contains 4,4′-bipyridine ligands linking six-coordinate NiII ions. Each NiII ion is in an octahedral environment, coordinated by two aqua ligands, two (4-tolylsulfanyl)acetate ligands and two bridging 4,4′-bipyridine ligands, generating linear chains; π–π interactions between adjacent chains result in a layered structure. A twofold rotation axis runs through the Ni atom and along the bridging ligand.
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Nowbakht, Pegah, Mihai-Constantin S. Ionescu, Andreas Rohner, Christian P. Kalberer, Emmanuel Rossy, Lucia Mori, David Cosman, Gennaro De Libero, and Aleksandra Wodnar-Filipowicz. "Ligands for natural killer cell–activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias." Blood 105, no. 9 (May 1, 2005): 3615–22. http://dx.doi.org/10.1182/blood-2004-07-2585.
Full textAbstract:
AbstractNatural killer (NK) cell–mediated cytolytic activity against tumors requires the engagement of activating NK receptors by the tumor-associated ligands. Here, we have studied the role of NKG2D and natural cytotoxicity receptors (NCRs) in the recognition of human leukemia. To detect as-yet-unknown cell-surface molecules recognized by NCRs, we developed soluble forms of NKp30, NKp44, and NKp46 as staining reagents binding the putative cognate ligands. Analysis of UL16-binding protein-1 (ULBP1), ULBP2, and ULBP3 ligands for NKG2D and of potential ligands for NKp30, NKp44, and NKp46 in healthy hematopoietic cells demonstrated the ligand-negative phenotype of bone marrow–derived CD34+ progenitor cells and the acquisition of cell-surface ligands during the course of myeloid differentiation. In acute myeloid leukemia (AML), leukemic blasts from approximately 80% of patients expressed very low levels of ULBPs and NCR-specific ligands. Treatment with differentiation-promoting myeloid growth factors, together with interferon-γ, upregulated cell-surface levels of ULBP1 and putative NCR ligands on AML blasts, conferring an increased sensitivity to NK cell–mediated lysis. We conclude that the ligand-negative/low phenotype in AML is a consequence of cell maturation arrest on malignant transformation and that defective expression of ligands for the activating NKG2D and NCR receptors may compromise leukemia recognition by NK cells.
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Balasanmugam, K., J. S. Hartman, J. M. Miller, and Z. Yuan. "Gas phase ligand substitution reactions in fast atom bombardment mass spectrometry: effects of ligand base strength and choice of matrix liquid in substitution reactions of difluoroborn cations." Canadian Journal of Chemistry 67, no. 4 (April 1, 1989): 685–88. http://dx.doi.org/10.1139/v89-104.
Full textAbstract:
Strongly basic amidine and guanidine ligands displace weaker-base ligands such as pyridine from D2BF2+ complexes in the gas phase in Fast Atom Bombardment mass spectrometry. The choice of protic vs. aprotic matrix liquid inhibits or promotes gas phase ligand substitution reactions. Keywords: ligand substitution, difluoroboron cations, FABMS.