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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1998-2-19
|
| pubmed:abstractText |
CGRP Y0-28-37 is known as a selective CGRP1 receptor antagonist. In order to elucidate the essential requirements for its receptor interaction, we performed a variety of systematic approaches by modifying the C-terminal segments CGRP Y0-28-37 and CGRP 27-37. N-Terminal and C-terminal segments have been synthesized, as well as chimeras which combine segments of CGRP, adrenomedullin, and amylin. Furthermore, we carried out an Ala scan, a Phe scan, a D-amino acid scan and a Pro scan of CGRP 27-37. Additionally, single amino acids were replaced by those with similar biophysical properties. Receptor binding studies of all analogs were performed at human neuroblastoma cells SK-N-MC, which selectively express the hCGRP1 receptor. On the basis of the obtained results, we synthesized a series of ligands with multiple amino acid replacements in order to optimize the exchange at each position. This approach yielded to a series of high affinity ligands, including [D31,P34,F35] CGRP 27-37 which exhibits a 100-fold increased affinity compared to the unmodified segment. So far, this is the smallest CGRP analog that shows affinity in the nanomolar range.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcitonin Gene-Related Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcitonin Gene-Related...,
http://linkedlifedata.com/resource/pubmed/chemical/calcitonin gene-related peptide...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
41
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
117-23
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:9438028-Amino Acid Sequence,
pubmed-meshheading:9438028-Animals,
pubmed-meshheading:9438028-Binding Sites,
pubmed-meshheading:9438028-Calcitonin Gene-Related Peptide,
pubmed-meshheading:9438028-Cell Membrane,
pubmed-meshheading:9438028-Humans,
pubmed-meshheading:9438028-Kinetics,
pubmed-meshheading:9438028-Microchemistry,
pubmed-meshheading:9438028-Molecular Sequence Data,
pubmed-meshheading:9438028-Neuroblastoma,
pubmed-meshheading:9438028-Oligopeptides,
pubmed-meshheading:9438028-Peptide Fragments,
pubmed-meshheading:9438028-Rats,
pubmed-meshheading:9438028-Receptors, Calcitonin Gene-Related Peptide,
pubmed-meshheading:9438028-Sequence Alignment,
pubmed-meshheading:9438028-Sequence Homology, Amino Acid,
pubmed-meshheading:9438028-Structure-Activity Relationship,
pubmed-meshheading:9438028-Tumor Cells, Cultured
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
From micromolar to nanomolar affinity: a systematic approach to identify the binding site of CGRP at the human calcitonin gene-related peptide 1 receptor.
|
| pubmed:affiliation |
Department of Pharmacy, ETH Zürich, Zürich, Switzerland.
|
| pubmed:publicationType |
Journal Article
|