Linked Life Data

2174509

Source:http://linkedlifedata.com/resource/pubmed/id/2174509

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1991-1-17
pubmed:abstractText
A series of residue 3-modified analogs of the cyclic, delta-opioid receptor-selective, dermorphin-like tetrapeptide Tyr-D-Cys-Phe-D-Pen and the corresponding residue 4-modified analog of the related delta receptor-selective cyclic pentapeptide [D-Pen2,D-Pen5] enkephalin were synthesized and evaluated in opioid receptor binding assays and in the in vitro mouse vas deferens (MVD) bioassay. In both series, substitutions that would be expected to alter the orientation of the phenylalanine-substituted aromatic side chain relative to the rest of the peptide, due to changes in the conformation of the peptide backbone, had deleterious effects on binding affinity and MVD potency. In general, these adverse effects were more pronounced in the pentapeptide series, owing, most likely, to the greater rigidity and, therefore, reduced susceptibility to conformational perturbation of the tetrapeptides. Substitution of phenylalanine by p-fluorophenylalanine enhances binding affinity in the pentapeptide series, consistent with previous observations in the enkephalins, but is without effect on binding in the tetrapeptide series. Substitution of phenylalanine by homophenylalanine, which alters the relationship of the aromatic phenyl ring to the remainder of the peptide by inserting an additional methylene group between the aromatic moiety and the backbone, greatly reduces binding affinity and MVD potency in the pentapeptide. The corresponding modification in the tetrapeptide series has little effect on delta receptor binding affinity and MVD potency and enhances binding to mu opioid receptors. Several possible interpretations of these results are discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
924-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Cyclic dermorphin-like tetrapeptides with delta-opioid receptor selectivity. 3. Effect of residue 3 modification on in vitro opioid activity.
pubmed:affiliation
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't