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Curr Opin Struct Biol. 1998 Aug;8(4):451-8.

Redesigning small molecule-protein interfaces.

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ARIAD Pharmaceuticals Inc, Cambridge, MA 02139, USA.


Several recent reports have described the rational redesign of small molecule-protein interfaces, generating modified ligands that interact only with suitably mutated proteins. These studies provide powerful reagents for specifically manipulating engineered proteins inside cells, as well as general insights into the factors underlying the binding affinity and specificity of small molecules in general. Progress this year includes the development of allele-specific inhibitors of Src-family tyrosine kinases and the crystal structure determination of a remodeled FKBP-ligand interface.

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