Linked Life Data

18324760

Source:http://linkedlifedata.com/resource/pubmed/id/18324760

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2008-4-8
pubmed:abstractText
Angiotensin-converting enzyme 2 (ACE2), a recently identified human homologue of angiotensin-converting enzyme, is a zinc metallocarboxypeptidase which may play a unique role in cardiovascular and renal function. Here we report the discovery of potent and selective inhibitors of ACE2, which have been identified by evaluating a series of phosphinic di- and tripeptides of the general formula: Z-Xaa(PO 2-CH 2)YaaOH and Ac-Zaa-Xaa(PO 2-CH 2)YaaOH. The most potent inhibitor in this series is a tripeptide that displays a K i value of 0.4 nM toward ACE2 and is 3 orders of magnitude less potent toward carboxypeptidase A. Phosphinic tripeptides exhibit high potency exclusively when the Xaa position is occupied by a pseudoproline. A model of interaction between one inhibitor of this series and ACE2 suggests that the critical role played by a proline in inhibitors, but also for substrates hydrolysis, may rely on the presence of Tyr (510) in the ACE2 active site.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2216-26
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Development of potent and selective phosphinic peptide inhibitors of angiotensin-converting enzyme 2.
pubmed:affiliation
Department of Chemistry, Laboratory of Organic Chemistry, University of Athens, Panepistimiopolis Zografou 15771, Athens, Greece.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't