Probing Protein Surfaces: QSAR Analysis with Helix Mimetics

Valeria Azzarito; Philip Rowell; Anna Barnard; Thomas A. Edwards; Andrew Macdonald; Stuart L. Warriner; Andrew J. Wilson

doi:10.1002/cbic.201500504

Probing Protein Surfaces: QSAR Analysis with Helix Mimetics

Valeria Azzarito^*, Philip Rowell, Anna Barnard, Thomas A. Edwards, Andrew Macdonald, Stuart L. Warriner, Andrew J. Wilson

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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. Rationalising behaviour: Using a helix mimetic based on an oligoamide scaffold, we have exploited a modular synthesis to access compounds that can readily be used to understand the noncovalent determinants of hDM2 recognition by cell-active p53/hDM2 inhibitors.

Original language	English
Pages (from-to)	768-773
Number of pages	6
Journal	ChemBioChem
Volume	17
Issue number	8
DOIs	https://doi.org/10.1002/cbic.201500504
Publication status	Published - 15 Apr 2016

Bibliographical note

Funding Information:
This work was supported by the European Research Council [ERCStG- 240324] and [ERC-PoC-632207] and The Wellcome Trust [102577/Z/13/Z] (to P.R.). The authors thank Dr. Jennifer Miles for protein expression and purification.

Publisher Copyright:
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Keywords

chemical biology
foldamers
helix mimetics
p53/hDM2
protein-protein interactions

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Organic Chemistry

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10.1002/cbic.201500504

Cite this

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title = "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. Rationalising behaviour: Using a helix mimetic based on an oligoamide scaffold, we have exploited a modular synthesis to access compounds that can readily be used to understand the noncovalent determinants of hDM2 recognition by cell-active p53/hDM2 inhibitors.",

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note = "Funding Information: This work was supported by the European Research Council [ERCStG- 240324] and [ERC-PoC-632207] and The Wellcome Trust [102577/Z/13/Z] (to P.R.). The authors thank Dr. Jennifer Miles for protein expression and purification. Publisher Copyright: {\textcopyright} 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.",

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doi = "10.1002/cbic.201500504",

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AU - Azzarito, Valeria

AU - Rowell, Philip

AU - Barnard, Anna

AU - Edwards, Thomas A.

AU - Macdonald, Andrew

AU - Warriner, Stuart L.

AU - Wilson, Andrew J.

N1 - Funding Information: This work was supported by the European Research Council [ERCStG- 240324] and [ERC-PoC-632207] and The Wellcome Trust [102577/Z/13/Z] (to P.R.). The authors thank Dr. Jennifer Miles for protein expression and purification. Publisher Copyright: © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2016/4/15

Y1 - 2016/4/15

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AB - 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. Rationalising behaviour: Using a helix mimetic based on an oligoamide scaffold, we have exploited a modular synthesis to access compounds that can readily be used to understand the noncovalent determinants of hDM2 recognition by cell-active p53/hDM2 inhibitors.

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Probing Protein Surfaces: QSAR Analysis with Helix Mimetics

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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