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Issue 4, 2015
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Stereocontrolled protein surface recognition using chiral oligoamide proteomimetic foldamers

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Abstract

The development of foldamers capable of selective molecular recognition of solvent exposed protein surfaces represents an outstanding challenge in supramolecular chemical biology. Here we introduce an oligoamide foldamer with well-defined conformation that bears all the hallmarks of an information rich oligomer. Specifically, the foldamer recognizes its target protein hDM2 leading to inhibition of its protein–protein interaction with p53 in a manner that depends upon the composition, spatial projection and stereochemistry of functional groups appended to the scaffold. Most significantly, selective inhibition of p53/hDM2 can be achieved against four other targets and the selectivity for p53/hDM2 inhibition versus Mcl-1/NOXA-B inhibition is critically dependent upon the stereochemistry of the helix mimetic.

Graphical abstract: Stereocontrolled protein surface recognition using chiral oligoamide proteomimetic foldamers

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Publication details

The article was received on 17 Nov 2014, accepted on 29 Jan 2015 and first published on 30 Jan 2015


Article type: Edge Article
DOI: 10.1039/C4SC03559C
Citation: Chem. Sci., 2015,6, 2434-2443
  • Open access: Creative Commons BY-NC license
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    Stereocontrolled protein surface recognition using chiral oligoamide proteomimetic foldamers

    V. Azzarito, J. A. Miles, J. Fisher, T. A. Edwards, S. L. Warriner and A. J. Wilson, Chem. Sci., 2015, 6, 2434
    DOI: 10.1039/C4SC03559C

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