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Probing Protein Surfaces: QSAR Analysis with Helix Mimetics
Author(s) -
Azzarito Valeria,
Rowell Philip,
Barnard Anna,
Edwards Thomas A.,
Macdonald Andrew,
Warriner Stuart L.,
Wilson Andrew J.
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500504
Subject(s) - quantitative structure–activity relationship , helix (gastropod) , non covalent interactions , chemistry , scaffold , computational biology , protein–protein interaction , combinatorial chemistry , modular design , small molecule , stereochemistry , molecule , biochemistry , biology , computer science , hydrogen bond , organic chemistry , ecology , database , snail , operating system
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 h DM2 recognition by this series of cell‐active p53/ h DM2 inhibitors.