Selective and potent proteomimetic inhibitors of intracellular protein-protein interactions

Anna Barnard; Kérya Long; Heather L. Martin; Jennifer A. Miles; Thomas A. Edwards; Darren C. Tomlinson; Andrew Macdonald; Andrew J. Wilson

doi:10.1002/anie.201410810

Selective and potent proteomimetic inhibitors of intracellular protein-protein interactions

Anna Barnard, Kérya Long, Heather L. Martin, Jennifer A. Miles, Thomas A. Edwards, Darren C. Tomlinson, Andrew Macdonald^*, Andrew J. Wilson

^*Corresponding author for this work

Chemistry

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

74 Citations (Scopus)

Abstract

Inhibition of protein-protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed "proteomimetics", which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified.

Original language	English
Pages (from-to)	2960-2965
Number of pages	6
Journal	Angewandte Chemie - International Edition
Volume	54
Issue number	10
DOIs	https://doi.org/10.1002/anie.201410810
Publication status	Published - 2 Mar 2015

Bibliographical note

Publisher Copyright:
© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Keywords

Apoptosis
Foldamers
Helical structures
Peptidomimetics
Protein-protein interactions

ASJC Scopus subject areas

Catalysis
General Chemistry

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10.1002/anie.201410810

Cite this

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abstract = "Inhibition of protein-protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. α-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed {"}proteomimetics{"}, which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified.",

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AU - Barnard, Anna

AU - Long, Kérya

AU - Martin, Heather L.

AU - Miles, Jennifer A.

AU - Edwards, Thomas A.

AU - Tomlinson, Darren C.

AU - Macdonald, Andrew

AU - Wilson, Andrew J.

PY - 2015/3/2

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KW - Apoptosis

KW - Foldamers

KW - Helical structures

KW - Peptidomimetics

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Selective and potent proteomimetic inhibitors of intracellular protein-protein interactions

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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