Linked Life Data

14695826

Source:http://linkedlifedata.com/resource/pubmed/id/14695826

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 comparative NMR conformational analysis of three distinct tetrapeptide inhibitors of the Hepatitis C NS3 protease that differ at the 4-aryloxy-substituted P2 proline position was undertaken. Specifically, transferred nuclear Overhauser effect experiments in combination with restrained systematic conformational searches were used to characterize the orientation of the P2 aryl substituents of these inhibitors when bound to the NS3 protease. Differences between free and bound conformations were also investigated. Analysis of the results allowed the design of a new P2 aromatic substituent, which significantly increased the potency of our inhibitors. The bound conformation of a specific competitive inhibitor having this novel P2 substituent is also described, along with a model of this inhibitor bound to the NS3 protease. This NS3 protease/inhibitor complex model also supports a hypothetical stabilization role for the P2 residue of the substrates and/or inhibitors and further elucidates the subtle details of the binding of the P2 residue of substrate-based inhibitors.
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
123-32
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
NMR structural characterization of peptide inhibitors bound to the Hepatitis C virus NS3 protease: design of a new P2 substituent.
pubmed:affiliation
Department of Chemistry, Boehringer Ingelheim (Canada) Ltd., Research & Development, 2100 Cunard Street, Laval, Québec, Canada H7S 2G5. ngoudreau@lav.boeringer-ingelheim.com
pubmed:publicationType
Journal Article