Linked Life Data

14695821

Source:http://linkedlifedata.com/resource/pubmed/id/14695821

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-12-29
pubmed:abstractText
A series of novel alpha-ketoamides incorporating stereoisomeric residues with different electronic properties at the P(1)'-position were synthesized to study the electronic requirements for inhibitor binding to the S(1)'-subsite of calpain I. The results of the study suggested the presence of an acidic amino acid residue at the S(1)'-subsite of calpain I. For example, ester 1a (Cbz-l-Leu-l-Phe-CO-d-Phe-OMe) was over 450-fold more potent than its carboxylic acid derivative 2a (Cbz-l-Leu-l-Phe-CO-d-Phe-OH). Additionally, amidino derivative 3a (Cbz-l-Leu-l-Phe-CONH-d-CH[C(NH)NH(2)]Bn) was about 6000-fold more potent than 2a. Furthermore, 4a (Cbz-l-Leu-l-Phe-CONHCH(2)Bn) was 12-fold less potent than its aza analogue 4b (Cbz-l-Leu-l-Phe-CONHNHBn). The results are consistent with the presence of an acidic amino acid residue at the S(1)'-subsite of calpain I. The acidic amino acid residue was found to be Glu261 via molecular modeling studies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
72-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Design, synthesis, molecular modeling studies, and calpain inhibitory activity of novel alpha-ketoamides incorporating polar residues at the P1'-position.
pubmed:affiliation
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. idonkor@utmem.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't