Novel pyrrolopyrimidine-based α-helix mimetics

Cell-permeable inhibitors of protein-protein interactions

Ji Hoon Lee, Qi Zhang, Sunhwan Jo, Sergio C. Chai, Misook Oh, Wonpil Im, Hua Lu, Hyun-Suk Lim

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

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 a-helix mimetics.

Original languageEnglish
Pages (from-to)676-679
Number of pages4
JournalJournal of the American Chemical Society
Volume133
Issue number4
DOIs
StatePublished - Feb 2 2011

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Proteins
Molecules
Fluorescence Polarization
Scaffolds
Rigidity
Libraries
Assays
Fluorescence
Polarization
pyrrolopyrimidine

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Novel pyrrolopyrimidine-based α-helix mimetics : Cell-permeable inhibitors of protein-protein interactions. / Lee, Ji Hoon; Zhang, Qi; Jo, Sunhwan; Chai, Sergio C.; Oh, Misook; Im, Wonpil; Lu, Hua; Lim, Hyun-Suk.

In: Journal of the American Chemical Society, Vol. 133, No. 4, 02.02.2011, p. 676-679.

Research output: Contribution to journalArticle

Lee, Ji Hoon ; Zhang, Qi ; Jo, Sunhwan ; Chai, Sergio C. ; Oh, Misook ; Im, Wonpil ; Lu, Hua ; Lim, Hyun-Suk. / Novel pyrrolopyrimidine-based α-helix mimetics : Cell-permeable inhibitors of protein-protein interactions. In: Journal of the American Chemical Society. 2011 ; Vol. 133, No. 4. pp. 676-679.
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