|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
2
|
|
pubmed:dateCreated |
2003-1-23
|
|
pubmed:abstractText |
1. The role of individual residues in the 8-18 helix of CGRP(8-37) in promoting high-affinity binding to CGRP(1) receptors expressed on rat L6 and human SK-N-MC cells has been examined. The relative potencies of various derivatives were estimated from their ability to inhibit the human alphaCGRP-mediated increase in cyclic AMP production and the binding of [(125)I]-human alphaCGRP. 2. Arg(11) and Arg(18) were replaced by serines to give [Ser(11,18)]CGRP(8-37). These bound with pKi values <6 to SK-N-MC cells and had apparent pA(2) values of 5.81+/-0.04 and 5.31+/-0.11 on SK-N-MC and L6 cells. CGRP(8-37) had a pKi of 8.22 on SK-N-MC cells and pK(b) values on the above cell lines of 8.95+/-0.04 and 8.76+/-0.04. 3. The arginines were replaced with glutamic acid residues. [Glu(11)]CGRP(8-37) had a pK(b) of 7.14+/-0.14 on SK-N-MC cells (pKi=7.05+/-0.05) and 6.99+/-0.08 on L6 cells. [Glu(18)]CGRP(8-37) had a pK(b) of 7.10+/-0.0.08 on SK-N-MC cells (pKi=6.91+/-0.23) and 7.12+/-0.09 on L6 cells. 4. Leu(12), Leu(15) and Leu(16) were replaced by benzoyl-phenylalanine (bpa) residues. On SK-N-MC cells, the apparent pA(2) values of [bpa(12)]-, [bpa(15)]- and [bpa(16)]CGRP(8-37) were respectively 7.43+/-0.23, 8.34+/-0.11 and 5.66+/-0.16 (pKi values of 7.14+/-0.17, 7.66+/-0.21 and <6): on L6 cells they were 7.96+/-0.36, 8.28+/-0.21 and 6.09+/-0.04 (all n=3). 5. It is concluded that the Arg(11) and Arg(18) are involved in specific electrostatic interactions with other residues, either on the CGRP(1) receptors or elsewhere on CGRP(8-37). Leu(16) is in a conformationally restricted site when CGRP(8-37) binds to CGRP(1) receptors, unlike Leu(12) and Leu(15).
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-10205004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-10696108,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-10711339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-11847213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-1313730,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-1319490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-1322087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-1336185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-1653835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-2177866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-2537579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-3264724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-3511529,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-7818539,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-7883029,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-8527874,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-8836775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-9222559,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-9301670,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-9605575,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-9620797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12540523-9756381
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jan
|
|
pubmed:issn |
0007-1188
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
138
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
325-32
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:12540523-Animals,
pubmed-meshheading:12540523-Calcitonin Gene-Related Peptide,
pubmed-meshheading:12540523-Cyclic AMP,
pubmed-meshheading:12540523-Dose-Response Relationship, Drug,
pubmed-meshheading:12540523-Humans,
pubmed-meshheading:12540523-Hydrogen Bonding,
pubmed-meshheading:12540523-Peptide Fragments,
pubmed-meshheading:12540523-Protein Binding,
pubmed-meshheading:12540523-Protein Structure, Secondary,
pubmed-meshheading:12540523-Rats,
pubmed-meshheading:12540523-Receptors, Calcitonin Gene-Related Peptide,
pubmed-meshheading:12540523-Static Electricity,
pubmed-meshheading:12540523-Stereoisomerism,
pubmed-meshheading:12540523-Tumor Cells, Cultured
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
The role of the 8-18 helix of CGRP8-37 in mediating high affinity binding to CGRP receptors; coulombic and steric interactions.
|
|
pubmed:affiliation |
Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
