Inhibition of a prolyl hydroxylase domain (PHD) by substrate analog peptides |
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| Authors: | Kwon Hyuk Sung Choi Yien Kyoung Kim Jeong Won Park Yong Keun Yang Eun Gyeong Ahn Dae-Ro |
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| Institution: | a Biomedical Research Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea
b Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, 5-ga Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea |
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| Abstract: | Oxygen dependent degradation of hypoxia-inducible factor (HIF)-1α is triggered with hydroxylation by proline hydroxylase domain 2 (PHD2) under normoxic conditions. Some of previously developed PHD2 inhibitors show a considerable potency against factor inhibiting HIF (FIH), the HIF asparagine hydroxylase. For specific inhibition of PHD2, we have synthesized peptides containing 556-575 residues of HIF-1α with modifications at the Pro-564 and examined their inhibitory effect against PHD2. Adopting fluorescence polarization-based assays, we evaluated inhibitory potency of the peptides and selected potent inhibitors. These PHD2 inhibitor peptides showed no significant potency against FIH, demonstrating their specific inhibitory effect on PHD2. |
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| Keywords: | HIF-1α PHD2 Substrate analog peptides Peptide inhibitors Hypoxia |
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