Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-12-14
pubmed:abstractText
The sequence of a cholecystokinin (CCK) related peptide was modified to obtain analogues, which interact selectively either with CCK-B, or with delta-opioid receptors. Two kinds of peptides were designed, namely, the cyclic peptides of the H-Tyr-cyclo (D-Pen-Gly-Trp-L/D-3-transmercaptoproline)-Asp-Phe-NH2 sequence (compounds 1a and 1b, respectively), and the linear peptides of the H-Tyr-D-Val-Gly-Trp-L/D-3-trans-methylmercaptoproline-Asp-Phe- NH2 sequence (compounds 2a and 2b, respectively). The only difference between the chemical structures of the linear analogues compared to the cyclic ones is that one covalent bond has been eliminated and a sulfur atom is replaced by a methyl group. Molecular modeling showed that, among low-energy conformers of cyclic compounds 1, there are three-dimensional structures compatible to the model for delta-receptor-bound conformer, suggested earlier [G. V. Nikiforovich, V.J. Hruby, O. Prakash, and C.A. Gehrig (1991) Biopolymers, vol. 31, pp. 941-955]. Results of binding assays fully supported the rationale for the design of compounds 1 and 2. The cyclic analogue 1a has Ki values of 4.5 and > 5000 nM at delta- and mu-opioid receptors, respectively; and IC50 values of 1.6 and > 10,000 nM for CCK-A and CCK-B receptors, respectively. The results of this study demonstrate a possibility to redirect a peptide sequence that interacts with one type of receptors (CCK-B receptors) toward interaction with another type (delta-opioid receptors) belonging to a different physiological system. This redirection could be performed by changing the conformational properties of the peptide with very minimal changes in its chemical structure.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-3525
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
439-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7578939-Amino Acid Sequence, pubmed-meshheading:7578939-Animals, pubmed-meshheading:7578939-Cell Line, pubmed-meshheading:7578939-Cholecystokinin, pubmed-meshheading:7578939-Humans, pubmed-meshheading:7578939-Kinetics, pubmed-meshheading:7578939-Ligands, pubmed-meshheading:7578939-Male, pubmed-meshheading:7578939-Models, Molecular, pubmed-meshheading:7578939-Molecular Sequence Data, pubmed-meshheading:7578939-Narcotics, pubmed-meshheading:7578939-Oligopeptides, pubmed-meshheading:7578939-Pancreas, pubmed-meshheading:7578939-Protein Conformation, pubmed-meshheading:7578939-Rats, pubmed-meshheading:7578939-Rats, Wistar, pubmed-meshheading:7578939-Receptors, Cholecystokinin, pubmed-meshheading:7578939-Receptors, Opioid, delta, pubmed-meshheading:7578939-Structure-Activity Relationship
pubmed:year
1995
pubmed:articleTitle
Conformationally readdressed CCK-B/delta-opioid peptide ligands.
pubmed:affiliation
Center for Molecular Design, Washington University, School of Medicine, St. Louis, MO 63130, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.