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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1994-7-7
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pubmed:abstractText |
Previous structure-activity studies on a series of CCK-A selective tetrapeptide agonists, typified by A-71623 (Boc-Trp-Lys(CONH-Ph-o-Me)-Asp-(N-Me)Phe-NH2), have shown that replacement of the Lys(N epsilon-carbamoyl) substituent with N epsilon-acyl substituents resulted in partial agonists with moderate to high affinities for the CCK-A receptor and that replacement of the C-terminal dipeptide with either (N-Me)Asp-Phe or (N-Me)Asp-(N-Me)Phe was highly favorable to in vitro and in vivo CCK activity. The present study demonstrates that although analogues in the epsilon-amide series that are N-methylated at the Phe position are weakly active or inactive in an in vivo rat appetite suppression assay, incorporation of (N-Me)Asp or (N-Me)Asp-(N-Me)Phe modifications in this series results in analogues with markedly improved in vivo activity. In in vitro assays, there is minimal effect of N-methylation pattern on binding affinity, whereas there is a trend toward improved functional activity in the phosphatidylinositol hydrolysis assay in analogues containing (N-Me)Asp.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
1569-71
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8201591-Amino Acid Sequence,
pubmed-meshheading:8201591-Animals,
pubmed-meshheading:8201591-Appetite Depressants,
pubmed-meshheading:8201591-Aspartic Acid,
pubmed-meshheading:8201591-Cerebral Cortex,
pubmed-meshheading:8201591-Cholecystokinin,
pubmed-meshheading:8201591-Eating,
pubmed-meshheading:8201591-Guinea Pigs,
pubmed-meshheading:8201591-Hydrolysis,
pubmed-meshheading:8201591-Lysine,
pubmed-meshheading:8201591-Methylation,
pubmed-meshheading:8201591-Molecular Sequence Data,
pubmed-meshheading:8201591-Oligopeptides,
pubmed-meshheading:8201591-Pancreas,
pubmed-meshheading:8201591-Phosphatidylinositols,
pubmed-meshheading:8201591-Rats,
pubmed-meshheading:8201591-Receptors, Cholecystokinin,
pubmed-meshheading:8201591-Structure-Activity Relationship,
pubmed-meshheading:8201591-Tetragastrin
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pubmed:year |
1994
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pubmed:articleTitle |
CCK-A-selective tetrapeptides containing lys(N epsilon)-amide residues: favorable in vivo and in vitro effects of N-methylation at the aspartyl residue.
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pubmed:affiliation |
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.
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pubmed:publicationType |
Journal Article,
Comparative Study
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