title: Inhibition of a prolyl hydroxylase domain (PHD) by substrate analog peptides.
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.
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors.forename: Hyuk Sung
authors.initials: HS
authors.lastname: Kwon
authors.forename: Yien Kyoung
authors.initials: YK
authors.lastname: Choi
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Yong Keun
authors.initials: YK
authors.lastname: Park
authors.forename: Eun Gyeong
authors.initials: EG
authors.lastname: Yang
authors.forename: Dae-Ro
authors.initials: DR
authors.lastname: Ahn
mesh_terms: D000595:Amino Acid Sequence; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010455:Peptides; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases