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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
24
|
| pubmed:dateCreated |
1994-1-11
|
| pubmed:abstractText |
In order to study the contribution of the electronic, hydrophobic, and conformational properties of the amino acid residue at position 3 in deltorphin C on binding to delta and mu opioid receptors, a series of 5- and 6-membered ring and bicyclic amino acid replacements at position 3 were prepared by solution synthesis methods. In general, the substitutions were deleterious for high delta affinity (Ki delta) and delta selectivity (Ki mu/Ki delta). However, several notable exceptions were recognized: peptides containing the constrained, bicyclic structures Aic3 and (R or S) Atc3 enhanced delta affinity, but only the latter increased delta selectivity 4-fold (= 2475) relative to deltorphin C (= 661); at the other extreme, delta affinity of N alpha MePh3 fell 900-fold. Bioassays of [N alpha MePhe3]-, [(R or S)C alpha MePhe3]-, [Tic3]-, [Aic3]-, and [(R or S) Atc3]deltorphin C using guinea pig ileum (GPI) and mouse vas deferens (MVD) for mu and delta bioactivity, respectively, revealed a significant correlation (r = 0.916) between MVD bioactivity and delta binding in brain membranes. [(R or S)Atc3]deltorphin C also exhibited the highest biological selectivity (GPI/MVD) (= 3,522), which was 3-fold greater than that observed for deltorphin C. Molecular modelling of [N alpha MePhe3]- and [(S)Atc3]deltorphin C established that these amino acid replacements for Phe3 produce alterations in the backbone (phi,psi) and side-chain (chi 1,chi 2) dihedrals which critically affect the flexibility of the peptide and possibly limit accessible conformations for its alignment within the delta opioid receptor. The data provide evidence that the delta receptor is sensitive to changes in the composition, conformation, and orientation of the side chain of residue 3 of a linear opioid heptapeptide.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylalanine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Opioid, delta,
http://linkedlifedata.com/resource/pubmed/chemical/deltorphin I, Ala(2)-
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
26
|
| pubmed:volume |
36
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3748-56
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8254604-Amino Acid Sequence,
pubmed-meshheading:8254604-Animals,
pubmed-meshheading:8254604-Brain,
pubmed-meshheading:8254604-Guinea Pigs,
pubmed-meshheading:8254604-Ileum,
pubmed-meshheading:8254604-Male,
pubmed-meshheading:8254604-Mice,
pubmed-meshheading:8254604-Models, Molecular,
pubmed-meshheading:8254604-Molecular Sequence Data,
pubmed-meshheading:8254604-Molecular Structure,
pubmed-meshheading:8254604-Oligopeptides,
pubmed-meshheading:8254604-Peptide Fragments,
pubmed-meshheading:8254604-Phenylalanine,
pubmed-meshheading:8254604-Protein Conformation,
pubmed-meshheading:8254604-Rats,
pubmed-meshheading:8254604-Rats, Sprague-Dawley,
pubmed-meshheading:8254604-Receptors, Opioid, delta,
pubmed-meshheading:8254604-Structure-Activity Relationship,
pubmed-meshheading:8254604-Vas Deferens
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Phe3-substituted analogues of deltorphin C. Spatial conformation and topography of the aromatic ring in peptide recognition by delta opioid receptors.
|
| pubmed:affiliation |
Department of Pharmaceutical Science, University of Ferrara, Italy.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|