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Probing Protein Surfaces: QSAR Analysis with Helix Mimetics.

ABSTRACT: α-Helix-mediated protein-protein interactions (PPIs) are important targets for small-molecule inhibition; however, generic approaches to inhibitor design are in their infancy and would benefit from QSAR analyses to rationalise the noncovalent basis of molecular recognition by designed ligands. Using a helix mimetic based on an oligoamide scaffold, we have exploited the power of a modular synthesis to access compounds that can readily be used to understand the noncovalent determinants of hDM2 recognition by this series of cell-active p53/hDM2 inhibitors.

SUBMITTER: Azzarito V

PROVIDER: S-EPMC6591138 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Probing Protein Surfaces: QSAR Analysis with Helix Mimetics.

Azzarito Valeria V Rowell Philip P Barnard Anna A Edwards Thomas A TA Macdonald Andrew A Warriner Stuart L SL Wilson Andrew J AJ

Chembiochem : a European journal of chemical biology 20160121 8

α-Helix-mediated protein-protein interactions (PPIs) are important targets for small-molecule inhibition; however, generic approaches to inhibitor design are in their infancy and would benefit from QSAR analyses to rationalise the noncovalent basis of molecular recognition by designed ligands. Using a helix mimetic based on an oligoamide scaffold, we have exploited the power of a modular synthesis to access compounds that can readily be used to understand the noncovalent determinants of hDM2 rec ...[more]

PMID: 26690307

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