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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
16
|
| pubmed:dateCreated |
1993-9-24
|
| pubmed:abstractText |
The mechanism-based inactivation of human neutral endopeptidase 24.11 (NEP) was studied with N-[(R)-2-benzyl-5-cyano-4-oxopentanoyl]-L-phenylalanine (1) and its peptidic analogue, N(-)[N-(cyanoacetyl)-L-phenylalanyl]-L-phenylalanine (2). While both these active-site-directed molecules inactivate NEP, the related angiotensin-converting enzyme (ACE) is only inactivated by compound 2 [Ghosh et al. J. Med. Chem. 1992, 35, 4175-4179]. The selectivity in inactivation was addressed further by a comparative study of the interaction of compounds 1 and 2 with five other zinc proteases. The selective inactivation of NEP observed with the ketomethylene compound 1 suggests that the active site of NEP is less discriminating in its requirements for binding such substrate analogues as compared to ACE, a characteristic that may be exploited for designing specific mechanism-based inactivators for NEP. It is proposed that the inactivation is a result of NEP-catalyzed formation of ketenimine intermediates, which are subsequently trapped by an active-site nucleophile.
|
| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
6
|
| pubmed:volume |
36
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2408-11
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading | |
| pubmed:year |
1993
|
| pubmed:articleTitle |
A mechanism-based inactivation study of neutral endopeptidase 24.11.
|
| pubmed:affiliation |
Salk Biotechnology/Industrial Associates, Inc., La Jolla, California 92138.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|