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Probing Protein Surfaces: QSAR Analysis with Helix Mimetics.
Chembiochem. 2016 Apr 15; 17(8):768-73.C

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.

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Authors+Show Affiliations

Azzarito V
School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
Rowell P
Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
Barnard A
Department of Chemistry, Imperial College London, London, London, SW7 2AZ, UK. Institue of Chemical Biology, Imperial College London, London, SW7 2AZ, UK.
Edwards TA
Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
Macdonald A
Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
Warriner SL
School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. A.J.Wilson@leeds.ac.uk. Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. A.J.Wilson@leeds.ac.uk.
Wilson AJ
School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. S.L.Warrriner@leeds.ac.uk. Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. S.L.Warrriner@leeds.ac.uk.

MeSH

Dose-Response Relationship, DrugHumansLigandsModels, MolecularMolecular StructureProtein BindingProtein Structure, SecondaryProto-Oncogene Proteins c-mdm2Quantitative Structure-Activity RelationshipSmall Molecule LibrariesStructure-Activity RelationshipSurface PropertiesTumor Suppressor Protein p53

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26690307

Citation

Azzarito, Valeria, et al. "Probing Protein Surfaces: QSAR Analysis With Helix Mimetics." Chembiochem : a European Journal of Chemical Biology, vol. 17, no. 8, 2016, pp. 768-73.
Azzarito V, Rowell P, Barnard A, et al. Probing Protein Surfaces: QSAR Analysis with Helix Mimetics. Chembiochem. 2016;17(8):768-73.
Azzarito, V., Rowell, P., Barnard, A., Edwards, T. A., Macdonald, A., Warriner, S. L., & Wilson, A. J. (2016). Probing Protein Surfaces: QSAR Analysis with Helix Mimetics. Chembiochem : a European Journal of Chemical Biology, 17(8), 768-73. https://doi.org/10.1002/cbic.201500504
Azzarito V, et al. Probing Protein Surfaces: QSAR Analysis With Helix Mimetics. Chembiochem. 2016 Apr 15;17(8):768-73. PubMed PMID: 26690307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Probing Protein Surfaces: QSAR Analysis with Helix Mimetics. AU - Azzarito,Valeria, AU - Rowell,Philip, AU - Barnard,Anna, AU - Edwards,Thomas A, AU - Macdonald,Andrew, AU - Warriner,Stuart L, AU - Wilson,Andrew J, Y1 - 2016/01/21/ PY - 2015/10/02/received PY - 2015/12/23/entrez PY - 2015/12/23/pubmed PY - 2017/1/17/medline KW - chemical biology KW - foldamers KW - helix mimetics KW - p53/hDM2 KW - protein-protein interactions SP - 768 EP - 73 JF - Chembiochem : a European journal of chemical biology JO - Chembiochem VL - 17 IS - 8 N2 - 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. SN - 1439-7633 UR - https://www.unboundmedicine.com/medline/citation/26690307/Probing_Protein_Surfaces:_QSAR_Analysis_with_Helix_Mimetics_ DB - PRIME DP - Unbound Medicine ER -