ArticleChemical biology & drug design2013
Optimization of CD4/gp120 inhibitors by thermodynamic-guided alanine-scanning mutagenesis.
Article in Chemical biology & drug design, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Structural and Functional Characterization of Indane-Core CD4-Mimetic Compounds Substituted with Heterocyclic Amines.ACS medicinal chemistry letters · 2023Article
- Identification of gp120 Residue His105 as a Novel Target for HIV-1 Neutralization by Small-Molecule CD4-Mimics.ACS medicinal chemistry letters · 2021Article
- Binding Thermodynamics to Intrinsically Disordered Protein Domains.Methods in molecular biology (Clifton, N.J.) · 2020Article
- In Silico Identification of Novel Aromatic Compounds as Potential HIV-1 Entry Inhibitors Mimicking Cellular Receptor CD4.Viruses · 2019Article
- DisruPPI: structure-based computational redesign algorithm for protein binding disruption.Bioinformatics (Oxford, England) · 2018Article
- Article
- Computational identification of novel entry inhibitor scaffolds mimicking primary receptor CD4 of HIV-1 gp120.Journal of molecular modeling · 2017Article
- Computational Evaluation of HIV-1 gp120 Conformations of Soluble Trimeric gp140 Structures as Targets for de Novo Docking of First- and Second-Generation Small-Molecule CD4 Mimics.Journal of chemical information and modeling · 2016Article
- Small-Molecule CD4-Mimics: Structure-Based Optimization of HIV-1 Entry Inhibition.ACS medicinal chemistry letters · 2016Article
- Double Variational Binding--(SMILES) Conformational Analysis by Docking Mechanisms for Anti-HIV Pyrimidine Ligands.International journal of molecular sciences · 2015Article
- Computational Design of Hypothetical New Peptides Based on a Cyclotide Scaffold as HIV gp120 Inhibitor.PloS one · 2015Article
- CD4-mimetic small molecules sensitize human immunodeficiency virus to vaccine-elicited antibodies.Journal of virology · 2014Article
- Structure-based design, synthesis and validation of CD4-mimetic small molecule inhibitors of HIV-1 entry: conversion of a viral entry agonist to an antagonist.Accounts of chemical research · 2014Review
- Structure-Based Design and Synthesis of an HIV-1 Entry Inhibitor Exploiting X-Ray and Thermodynamic Characterization.ACS medicinal chemistry letters · 2013Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
As protein/protein interactions usually trigger signalling processes, inhibitors of those interactions must preclude protein binding without eliciting the signalling process themselves. To accomplish those goals, small molecules need to target those protein residues that contribute the most to binding (binding hotspots) without disturbing those residues that initiate signalling processes (allosteric hotspots). The availability of a blueprint identifying binding and allosteric hotspots will significantly aid inhibitor design and optimization. In this study, we show that in some situations the blueprint can be constructed by combining the standard technique of alanine-scanning mutagenesis with isothermal titration calorimetry (ITC). We demonstrate the approach by developing the combined binding and allosteric hotspots blueprint for CD4/gp120, the initial interaction leading to HIV-1 cell infection. A major finding of these studies is that not all binding hotspots are allosteric hotspots opening the possibility for the rational design of inhibitors and antagonist or agonist modulators.
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