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Evaluation of functional groups on amino acids in cyclic tetrapeptides in histone deacetylase inhibition.
MedLine Citation:
PMID:  21638021     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The naturally occurring cyclic tetrapeptide, chlamydocin, originally isolated from fungus Diheterospora chlamydosphoria, consists of α-aminoisobutyric acid, L: -phenylalanine, D: -proline and an unusual amino acid (S)-2-amino-8-((S)-oxiran-2-yl)-8-oxooctanoic acid (Aoe) and inhibits the histone deacetylases (HDACs), a class of regulatory enzymes. The epoxyketone moiety of Aoe is the key functional group for inhibition. The cyclic tetrapeptide scaffold is supposed to play important role for effective binding to the surface of enzymes. In place of the epoxyketone group, hydroxamic acid and sulfhydryl group have been applied to design inhibitor ligands to zinc atom in catalytic site of HDACs. In the research for more potent HDAC inhibitors, we replaced the epoxyketone moiety of Aoe with different functional groups and synthesized a series of chlamydocin analogs as HDAC inhibitors. Among the functional groups, methoxymethylketone moiety showed as potent inhibition as the hydroxamic acid. On the contrary, we confirmed that borate, trifruoromethylketone, and 2-aminoanilide are almost inactive in HDAC inhibition.
Authors:
Md Shahidul Islam; Mohammed P I Bhuiyan; Md Nurul Islam; Tienabe Kipassa Nsiama; Naoto Oishi; Tamaki Kato; Norikazu Nishino; Akihiro Ito; Minoru Yoshida
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-3
Journal Detail:
Title:  Amino acids     Volume:  -     ISSN:  1438-2199     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9200312     Medline TA:  Amino Acids     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Wakamatsu, Kitakyushu, 808-0196, Japan.
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