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Stereocontrolled protein surface recognition using chiral oligoamide proteomimetic foldamers.

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.

SUBMITTER: Azzarito V

PROVIDER: S-EPMC5646261 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Stereocontrolled protein surface recognition using chiral oligoamide proteomimetic foldamers.

Azzarito Valeria V Miles Jennifer A JA Fisher Julie J Edwards Thomas A TA Warriner Stuart L SL Wilson Andrew J AJ

Chemical science 20150130 4

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 <i>h</i>DM2 leading to inhibition of its protein-protein interaction with p53 in a manner that depends upon the composition, spat ...[more]

PMID: 29308155

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