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Novel pyrrolopyrimidine-based ?-helix mimetics: cell-permeable inhibitors of protein?protein interactions.

ABSTRACT: There is considerable interest in developing non-peptidic, small-molecule ?-helix mimetics to disrupt ?-helix-mediated protein?protein interactions. Herein, we report the design of a novel pyrrolopyrimidine-based scaffold for such ?-helix mimetics with increased conformational rigidity. We also developed a facile solid-phase synthetic route that is amenable to divergent synthesis of a large library. Using a fluorescence polarization-based assay, we identified cell-permeable, dual MDMX/MDM2 inhibitors, demonstrating that the designed molecules can act as ?-helix mimetics.

SUBMITTER: Lee JH

PROVIDER: S-EPMC3079198 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Novel pyrrolopyrimidine-based α-helix mimetics: cell-permeable inhibitors of protein−protein interactions.

Lee Ji Hoon JH Zhang Qi Q Jo Sunhwan S Chai Sergio C SC Oh Misook M Im Wonpil W Lu Hua H Lim Hyun-Suk HS

Journal of the American Chemical Society 20110201 4

There is considerable interest in developing non-peptidic, small-molecule α-helix mimetics to disrupt α-helix-mediated protein−protein interactions. Herein, we report the design of a novel pyrrolopyrimidine-based scaffold for such α-helix mimetics with increased conformational rigidity. We also developed a facile solid-phase synthetic route that is amenable to divergent synthesis of a large library. Using a fluorescence polarization-based assay, we identified cell-permeable, dual MDMX/MDM2 inhib ...[more]

PMID: 21171592

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