A multivalent peptide as an activator of hypoxia inducible factor-1a

Title
A multivalent peptide as an activator of hypoxia inducible factor-1a
Authors
권혁성박지애박용근안대로
Keywords
Hypoxia-inducible factor; Peptide inhibitor; VBC; Multivalent peptide inhibitor; VEGF
Issue Date
2013-03
Publisher
Bioorganic & medicinal chemistry letters
Citation
VOL 23, NO 6, 1716-1719
Abstract
Hypoxia inducible factor-1α (HIF-1α) is a transcription factor found in mammalian cells under hypoxia. While HIF-1α in hypoxia translocates to the nucleus where it transcribes the target genes including vascular endothelial growth factor (VEGF) mRNA, HIF-1α is degraded under normoxia, which involves its proline hydroxylation and subsequent binding to the von Hippel–Lindau protein-Elongin B-Elogin C (VBC) complex. Previously, peptide inhibitors against this interaction between hydroxylated HIF-1α and VBC have been developed to stabilize the transcriptional activity of HIF-1α by preventing the degradation of the protein even under normoxia. Despite the specific inhibition by these peptides, their poor inhibition potency needs to be improved for further clinical application. In this work, we have designed and prepared a streptavidin-based multivalent peptide inhibitor against the HIF-1α–VBC complexation. We have evaluated the potency of the multivalent peptide in terms of stabilization of HIF-1α and the downstream effect. As the result, we have found that the inhibitor showed about 13-fold lowered IC50 value compared with that of the corresponding monovalent peptide, thereby activating HIF-1α and leading to up-regulation of VEGF protein at the cellular level.
URI
http://pubs.kist.re.kr/handle/201004/46365
ISSN
0960894X
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KIST Publication > Article
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