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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3-4
|
| pubmed:dateCreated |
1996-2-8
|
| pubmed:abstractText |
We have refined the 1H NMR-based conformations of the mu-opioid receptor selective peptides related to somatostatin of general formula Xxx-Yyy1-Cys-Zzz-D-Trp-Lys(Orn)5-Thr-Pen-Thr8- NH2, where Xxx, Yyy, Zzz are 0, D-Phe and Tyr for 1; 0, D-Tic and Tyr for 2; Gly, D-Tic and Tyr for 3; and 0, D-Phe and Tic for 4, respectively, (Kazmierski et al., J. Am. Chem. 113, 2275-2283), using a molecular-dynamics approach. We present evidence that the NMR data are compatible with beta II'-, gamma- and gamma'-turns for the central tetrapeptide Tyr-D-Trp-Lys/Orn-Thr. Based on detailed structural and topographical considerations, we suggest that the mu-opioid receptor selectivity of 2 is due to a particular spatial arrangement of aromatic side chains of D-Tic1 and Tyr3 (7.5 A), and that the opioid receptor recognition domain is located in the N-terminal part of the peptide while the somatostatin receptor recognition domain is determined by the central, turn forming part of this class of cyclic peptides. A model for a mu-opioid selective ligand has emerged from these studies that shows excellent structural similarities to rigid opioid alkaloids.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:issn |
0367-8377
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
46
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
265-78
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:8537180-Amino Acid Sequence,
pubmed-meshheading:8537180-Animals,
pubmed-meshheading:8537180-Brain,
pubmed-meshheading:8537180-Chemistry, Physical,
pubmed-meshheading:8537180-Computer Simulation,
pubmed-meshheading:8537180-Magnetic Resonance Spectroscopy,
pubmed-meshheading:8537180-Models, Molecular,
pubmed-meshheading:8537180-Molecular Sequence Data,
pubmed-meshheading:8537180-Molecular Structure,
pubmed-meshheading:8537180-Physicochemical Phenomena,
pubmed-meshheading:8537180-Protein Conformation,
pubmed-meshheading:8537180-Rats,
pubmed-meshheading:8537180-Receptors, Opioid, mu,
pubmed-meshheading:8537180-Receptors, Somatostatin,
pubmed-meshheading:8537180-Somatostatin,
pubmed-meshheading:8537180-Structure-Activity Relationship,
pubmed-meshheading:8537180-Thermodynamics
|
| pubmed:articleTitle |
A topographical model of mu-opioid and brain somatostatin receptor selective ligands. NMR and molecular dynamics studies.
|
| pubmed:affiliation |
Department of Chemistry, University of Arizona, Tucson, USA.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|