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

doi:10.1021/ja9082864

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

Chemistry

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	941-943
Number of pages	3
Journal	Journal of the American Chemical Society
Volume	132
Issue number	3
DOIs	https://doi.org/10.1021/ja9082864
State	Published - 2010

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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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.",

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AU - Henchey, Laura K.

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AU - Olenyuk, Bogdan Z.

AU - Arora, Paramjit S.

PY - 2010

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AB - (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.

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

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