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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1992-8-14
|
| pubmed:databankReference | |
| pubmed:abstractText |
In these structure activity studies, the 46 analogs of the 27-amino-acid form of the pituitary-adenylate-cyclase-activating peptide, PACAP(1-27), and the 38-amino-acid form, PACAP(1-38), were either monosubstituted or bisubstituted at positions 1-3, 20 and 21 or N-terminally shortened. All analogs were compared on human neuroblastoma NB-OK-1 cell membranes for their ability to occupy 125I-[AcHis1]PACAP(1-27)-labelled receptors (AcHis, N alpha-acetylhistidine) and to activate adenylate cyclase (in terms of potency and intrinsic activity). The monophasic slope of dose/effect curves on both parameters suggested interaction with one class of PACAP receptor. Residues 28-38 in the C-terminally extended peptide, PACAP(1-38), played a favorable role in recognition, in that receptors coupled to adenylate cyclase were, in general, more sensitive to PACAP(1-38) analogs than to the corresponding PACAP(1-27) analogs. At variance with PACAP(6-27), PACAP(6-38) was well recognized and acted as a potent competitive antagonist (Ki 1.5 nM). Residues 1-3 were all important in enzyme activation: modification of the beta-turn potential gave full agonists (the LAla2 and DAla2 derivatives) or partial agonists (LPhe2 and DPhe2; LArg2 and DArg2; Glu3 and Asn3). Finally, a proper alpha-helix was also important: the combined substitution of Lys21/Lys22 by Gly21/Gly22 decreased the binding affinity sharply.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Pituitary Adenylate...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Pituitary Adenylate...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Pituitary Hormone
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0014-2956
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
207
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
239-46
|
| pubmed:dateRevised |
2007-7-23
|
| pubmed:meshHeading |
pubmed-meshheading:1321043-Adenylate Cyclase,
pubmed-meshheading:1321043-Amino Acid Sequence,
pubmed-meshheading:1321043-Binding, Competitive,
pubmed-meshheading:1321043-Cell Membrane,
pubmed-meshheading:1321043-Enzyme Activation,
pubmed-meshheading:1321043-Humans,
pubmed-meshheading:1321043-Kinetics,
pubmed-meshheading:1321043-Molecular Sequence Data,
pubmed-meshheading:1321043-Neuroblastoma,
pubmed-meshheading:1321043-Neuropeptides,
pubmed-meshheading:1321043-Peptide Fragments,
pubmed-meshheading:1321043-Pituitary Adenylate Cyclase-Activating Polypeptide,
pubmed-meshheading:1321043-Receptors, Cell Surface,
pubmed-meshheading:1321043-Receptors, Pituitary Adenylate Cyclase-Activating...,
pubmed-meshheading:1321043-Receptors, Pituitary Hormone,
pubmed-meshheading:1321043-Sequence Homology, Nucleic Acid,
pubmed-meshheading:1321043-Signal Transduction,
pubmed-meshheading:1321043-Structure-Activity Relationship,
pubmed-meshheading:1321043-Tumor Cells, Cultured
|
| pubmed:year |
1992
|
| pubmed:articleTitle |
Structural requirements for the occupancy of pituitary adenylate-cyclase-activating-peptide (PACAP) receptors and adenylate cyclase activation in human neuroblastoma NB-OK-1 cell membranes. Discovery of PACAP(6-38) as a potent antagonist.
|
| pubmed:affiliation |
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|