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Towards more drug-like proteomimetics: two-faced, synthetic ?-helix mimetics based on a purine scaffold.

ABSTRACT: Mimicry of two faces of an ?-helix might yield more potent and more selective inhibitors of aberrant, helix-mediated protein-protein interactions (PPI). Herein, we demonstrate that a 2,6,9-tri-substituted purine is capable of disrupting the Mcl-1-Bak-BH3 PPI through effective mimicry of key residues on opposing faces of the Bak-BH3 ?-helix.

SUBMITTER: Lanning ME

PROVIDER: S-EPMC4528301 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Towards more drug-like proteomimetics: two-faced, synthetic α-helix mimetics based on a purine scaffold.

Lanning M E ME Wilder P T PT Bailey H H Drennen B B Cavalier M M Chen L L Yap J L JL Raje M M Fletcher S S

Organic & biomolecular chemistry 20150724 32

Mimicry of two faces of an α-helix might yield more potent and more selective inhibitors of aberrant, helix-mediated protein-protein interactions (PPI). Herein, we demonstrate that a 2,6,9-tri-substituted purine is capable of disrupting the Mcl-1-Bak-BH3 PPI through effective mimicry of key residues on opposing faces of the Bak-BH3 α-helix. ...[more]

PMID: 26204921

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