Source:http://linkedlifedata.com/resource/pubmed/id/15485556
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2004-10-15
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| pubmed:abstractText |
Glycine-9 and leucine-10 of substance P (SP) are critical for (NK)-1 receptor recognition and agonist activity. Propsi(Z)-CH=CH(CH3)-CONH)Leu (or Met) and Propsi((E)-CH=CH(CH3)-CONH)Leu (or Met) have been introduced in the sequence of SP, in order to restrict the conformational flexibility of the C-terminal tripeptide, Gly-Leu-Met-NH2, of SP. Propsi((Z)-CH=C(CH2CH(CH3)2)-CONH)Met-NH2, with an isobutyl substituent to mimic the Leu side-chain, was also incorporated in place of the C-terminal tripeptide. The substituted-SP analogs were tested for their affinity to human NK-1 receptor specific binding sites (NK-1M and NK-1m) and their potency to stimulate adenylate cyclase and phospholipase C in Chinese Hamster ovary (CHO) cells transfected with the human NK-1 receptor. The most potent SP analogs [Pro9psi((Z)CH=C(CH3)CONH)Leu10]SP and [Pro9psi ((E)CH=C(CH3)CONH)Leu10]SP, are about 100-fold less potent than SP on both binding sites and second messenger pathways. These vinylogous (Z)- or (E)-CH=C(CH3)- or (Z)-CH=C(CH2CH(CH3)2) moieties hamper the correct positioning of the C-terminal tripeptide of SP within both the NK-1M- and NK-1m-specific binding sites. The origin of these lower potencies is related either to an incorrect peptidic backbone conformation and/or an unfavorable receptor interaction of the methyl or isobutyl group.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chymotrypsin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Substance P
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1397-002X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
64
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
186-93
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| pubmed:dateRevised |
2005-11-17
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| pubmed:meshHeading |
pubmed-meshheading:15485556-Animals,
pubmed-meshheading:15485556-Binding Sites,
pubmed-meshheading:15485556-CHO Cells,
pubmed-meshheading:15485556-Chymotrypsin,
pubmed-meshheading:15485556-Cricetinae,
pubmed-meshheading:15485556-Cyclic AMP,
pubmed-meshheading:15485556-Glycine,
pubmed-meshheading:15485556-Humans,
pubmed-meshheading:15485556-Kinetics,
pubmed-meshheading:15485556-Magnetic Resonance Spectroscopy,
pubmed-meshheading:15485556-Models, Chemical,
pubmed-meshheading:15485556-Peptides,
pubmed-meshheading:15485556-Protein Binding,
pubmed-meshheading:15485556-Protein Conformation,
pubmed-meshheading:15485556-Protein Structure, Tertiary,
pubmed-meshheading:15485556-Receptors, Neurokinin-1,
pubmed-meshheading:15485556-Signal Transduction,
pubmed-meshheading:15485556-Substance P,
pubmed-meshheading:15485556-Transfection
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| pubmed:year |
2004
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| pubmed:articleTitle |
Incorporation of vinylogous scaffolds in the C-terminal tripeptide of substance P.
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| pubmed:affiliation |
Laboratoire de Chimie Organique Biomoléculaire, Institut Nancéien de Chimie Moléculaire, Université H. Poincaré, Vandoeuvre-les-Nancy Cedex, France.
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| pubmed:publicationType |
Journal Article
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