REDESIGNING SMALL MOLECULE-PROTEIN INTERFACES

Several recent reports have described the rational redesign of small m olecule-protein interfaces, generating modified ligands that interact only with suitably mutated proteins. These studies provide powerful re agents for specifically manipulating engineered proteins inside cells, as well as general insights into the factors underlying the binding a ffinity and specificity of small molecules in general. Progress this y ear includes the development of allele-specific inhibitors of Src-fami ly tyrosine kinases and the crystal structure determination of a remod eled FKBP-ligand interface.