Inhibition of hypoxia inducible factor 1-transcription coactivator interaction by a hydrogen bond surrogate α-helix

Laura K. Henchey, Swati Kushal, Ramin Dubey, Ross N. Chapman, Bogdan Z. Olenyuk, Paramjit S. Arora

Research output: Contribution to journalArticle

Abstract

(Chemical Equation Presented) Designed ligands that inhibit hypoxia-inducible gene expression could offer new tools for genomic research and, potentially, drug discovery efforts for the treatment of neovascularization in cancers. We report a stabilizedα-helix designed to target the binding interface between the C-terminal transactivation domain (C-TAD) of hypoxia-inducible factor 1α (HIF-1α) and cysteine-histidine rich region (CH1) of transcriptional coactivator CBP/p300. The synthetic helix disrupts the structure and function of this complex, resulting in a rapid downregulation of two hypoxia-inducible genes (VEGF and GLUT1) in cell culture.

Original languageEnglish (US)
Pages (from-to)941-943
Number of pages3
JournalJournal of the American Chemical Society
Volume132
Issue number3
DOIs
StatePublished - 2010

ASJC Scopus subject areas

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

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