|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
10
|
|
pubmed:dateCreated |
2008-5-21
|
|
pubmed:abstractText |
The naturally occurring phosphonotripeptide K-26 is a potent angiotensin converting enzyme (ACE) inhibitor containing an alpha-amino phosphonic acid analogue of tyrosine. Previous studies have demonstrated that canonical peptide analogues of K-26 are micromolar inhibitors of ACE. To ascertain the structure-activity relationships in this class of ACE inhibitory natural products, K-26 and eight analogues were chemically synthesized and evaluated. Phosphonyl substitution was found to be the critical determinant of activity, resulting in a 1500-fold increase in ACE inhibition versus carboxyl analogues. Secondarily, the absolute configuration of the terminal alpha-amino phosphonate and N-acetylation were found to significantly modulate ACE inhibitory activity.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
1464-3405
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
15
|
|
pubmed:volume |
18
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
3068-71
|
|
pubmed:dateRevised |
2011-9-26
|
|
pubmed:meshHeading |
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
Identification of ACE pharmacophore in the phosphonopeptide metabolite K-26.
|
|
pubmed:affiliation |
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
