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Novel Pyrrolopyrimidine-Based α-Helix Mimetics: Cell-Permeable Inhibitors of Protein−Protein Interactions

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journal contribution
posted on 02.02.2011 by Ji Hoon Lee, Qi Zhang, Sunhwan Jo, Sergio C. Chai, Misook Oh, Wonpil Im, Hua Lu, Hyun-Suk Lim
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 inhibitors, demonstrating that the designed molecules can act as α-helix mimetics.