Optimization of CD4/gp120 inhibitors by thermodynamic-guided alanine-scanning mutagenesis.

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 bind

SUBMITTER: Liu Y 

PROVIDER: S-EPMC3527665 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature