PMID- 21665470
OWN - NLM
STAT- MEDLINE
DCOM- 20111025
LR  - 20131121
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Linking)
VI  - 21
IP  - 14
DP  - 2011 Jul 15
TI  - Inhibition of a prolyl hydroxylase domain (PHD) by substrate analog peptides.
PG  - 4325-8
LID - 10.1016/j.bmcl.2011.05.050 [doi]
AB  - Oxygen dependent degradation of hypoxia-inducible factor (HIF)-1alpha 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-1alpha 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.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Kwon, Hyuk Sung
AU  - Kwon HS
AD  - Biomedical Research Institute, Korea Institute of Science and Technology, PO Box 
      131, Cheongryang, Seoul 130-650, Republic of Korea.
FAU - Choi, Yien Kyoung
AU  - Choi YK
FAU - Kim, Jeong Won
AU  - Kim JW
FAU - Park, Yong Keun
AU  - Park YK
FAU - Yang, Eun Gyeong
AU  - Yang EG
FAU - Ahn, Dae-Ro
AU  - Ahn DR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110524
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Peptides)
RN  - EC 1.14.11.2 (EGLN1 protein, human)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Enzyme Inhibitors/chemical synthesis/*chemistry/pharmacology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/chemistry
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases
MH  - Peptides/chemical synthesis/*chemistry/pharmacology
MH  - Procollagen-Proline Dioxygenase/*antagonists & inhibitors/metabolism
MH  - Substrate Specificity
EDAT- 2011/06/15 06:00
MHDA- 2011/10/26 06:00
CRDT- 2011/06/14 06:00
PHST- 2010/12/21 00:00 [received]
PHST- 2011/05/04 00:00 [revised]
PHST- 2011/05/17 00:00 [accepted]
PHST- 2011/06/14 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2011/10/26 06:00 [medline]
AID - S0960-894X(11)00679-2 [pii]
AID - 10.1016/j.bmcl.2011.05.050 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2011 Jul 15;21(14):4325-8. doi: 10.1016/j.bmcl.2011.05.050. 
      Epub 2011 May 24.