Premium
Inhibition of hypoxia‐inducible transcription factor complex with designed epipolythiodiketopiperazine
Author(s) -
Kushal Swati,
Wang Hui,
László Csaba F.,
Szábo Lajos Z.,
Olenyuk Bogdan Z.
Publication year - 2011
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21550
Subject(s) - chemistry , transcription factor , hypoxia (environmental) , hypoxia inducible factors , hypoxia inducible factor 1 , microbiology and biotechnology , biochemistry , oxygen , gene , organic chemistry , biology
Designed small molecule inhibitors of hypoxia‐inducible gene expression have potential to become new research tools for molecular biology, genetics and serve as leads to new therapeutics. We report design, synthesis evaluation of biological activity, and a preliminary mechanistic study of epipolythiodiketopiperazine (ETP) transcriptional antagonist that targets the interaction between the C‐terminal transactivation domain (C‐TAD) of hypoxia‐inducible factor 1α (HIF‐1α) and cysteine‐histidine rich region (CH1) of transcriptional coactivator p300/CBP. Our results indicate that in cultured cells synthetic ETP 3 disrupts the structure and function of this complex in a dose‐dependent manner, resulting in rapid downregulation of hypoxia‐inducible gene expression. © 2010 Wiley Periodicals, Inc. Biopolymers 95: 8–16, 2011.