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.
Keywords:
chemical biology; foldamers; helix mimetics; p53/hDM2; protein-protein interactions.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Dose-Response Relationship, Drug
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Humans
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Ligands
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Models, Molecular
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Molecular Structure
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Protein Binding / drug effects
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Protein Structure, Secondary
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Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-mdm2 / chemistry*
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Quantitative Structure-Activity Relationship*
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Small Molecule Libraries / chemical synthesis
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology
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Structure-Activity Relationship
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Surface Properties
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Tumor Suppressor Protein p53 / antagonists & inhibitors
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Tumor Suppressor Protein p53 / chemistry*
Substances
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Ligands
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Small Molecule Libraries
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Tumor Suppressor Protein p53
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2