Linked Life Data

11082703

Source:http://linkedlifedata.com/resource/pubmed/id/11082703

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2000-12-21
pubmed:abstractText
The studies on both structure-activity relationship study and identification of the target enzyme of novel nonpeptide aminopeptidase inhibitors with cyclic imide skeleton are reviewed. Some N-phenylphthalimide or N-phenylhomophthalimide derivative showed potent protease inhibitory activity in an assay system using human acute lymphoblastic leukemia cells, Molt-4, with alanin-4-methylcoumaryl-7-amide (ala-AMC) as a substrate. Especially, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22) (3) was found to be the most potent inhibitor and further it showed potent tumor-cell invasion inhibitory activity that is more effective than potent peptide aminopeptidase inhibitors such as bestatin (1) or actinonin (2). For the further investigation of this novel protease inhibitory activity, we have carried out the structural development of PIQ-22 (3) and it is assumed that tautomerism of imidobenzoylketone in cyclic imide structure may be related to the inhibitory activity. The requirement for the activity of electron donating groups such as NH2 or OH to the condensed phenyl ring in phthalimide inhibitors also supports this possibility. The target aminopeptidase of PIQ-22 was identified as puromycin-sensitive aminopeptidase (PSA), by N-terminal amino acid sequencing, and by comparison with chromatographic behavior and substrate-selectivity, and so on. Lineweaver-Burk plot showed that PSA is inhibited by PIQ-22 (3) in a noncompetitive manner while puromycin (83) and bestatin (1) inhibit PSA competitively.
pubmed:language
jpn
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0031-6903
pubmed:author
pubmed:issnType
Print
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
909-21
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
[Preparation of novel specific aminopeptidase inhibitors with a cyclic imide skeleton].
pubmed:affiliation
Institute of Molecular and Cellular Bioscience, University of Tokyo, Japan.
pubmed:publicationType
Journal Article, English Abstract, Review, Research Support, Non-U.S. Gov't