Modifications to the N-Terminus but Not the C-Terminus of Calcitonin Gene-Related Peptide(8-37) Produce Antagonists with Increased Affinity

2003 ◽  
Vol 46 (12) ◽  
pp. 2427-2435 ◽  
Author(s):  
D. David Smith ◽  
Shankar Saha ◽  
Guoyong Fang ◽  
Courtney Schaffert ◽  
David J. J. Waugh ◽  
...  
1995 ◽  
Vol 73 (7) ◽  
pp. 963-967 ◽  
Author(s):  
Roman Muff ◽  
Walter Born ◽  
Jan A. Fischer

Calcitonin, calcitonin gene related peptide, amylin, and adrenomedullin are structurally related polypeptides characterized by a six or seven amino acid ring structure linked by a disulfide bridge and an amidated C-terminus. They exhibit overlapping biological actions as a result of cross-reactivity between the different receptors. In this article, the respective receptors and G-protein-coupled postreceptor events are reviewed in relation to some of the biological actions of the peptides.Key words: adrenomedullin, amylin, calcitonin gene related peptide, cyclic AMP, receptors.


1990 ◽  
Vol 36 (7) ◽  
pp. 1288-1294 ◽  
Author(s):  
M Zaidi ◽  
R Seth ◽  
S I Girgis ◽  
C H Self

Abstract Calcitonin gene-related peptide (CGRP), a potent endogenous circulating vasodilator, is produced by the alternative splicing of the calcitonin/CGRP gene and is expressed mainly in neural and cardiovascular tissues. We recently reported a highly sensitive radioimmunoassay of CGRP, based on an antiserum recognizing the C-terminus of the molecule. We have also found that circulating immunoreactive CGRP is heterogeneous; thus we are unable to measure selectively the intact molecule with our one-site competitive approach. We therefore attempted to construct a two-site immunometric assay involving two antibodies, one that detects the C-terminus and another that recognizes the midregion of the molecule. To enhance assay sensitivity, we applied a colorimetric amplification system to this assay. This rapid, robust, and reproducible assay provides more nearly accurate estimates of circulating CGRP and offers a sensitive and more specific alternative to the radioimmunoassay, with advantages in speed, simplicity, and convenience.


1993 ◽  
Vol 291 (1) ◽  
pp. 205-210 ◽  
Author(s):  
J P O'Connell ◽  
S M Kelly ◽  
D P Raleigh ◽  
J A M Hubbard ◽  
N C Price ◽  
...  

alpha-Calcitonin-gene-related peptide (alpha CGRP) lacking its C-terminal phenylalaninamide residue was found not to bind to its receptor as did full-length (amidated) alpha CGRP. Investigation of the structure of these peptides by c.d. and n.m.r. revealed no significant difference, so it seemed that the effect of deleting the C-terminal phenylalaninamide on the biological activity of alpha CGRP was not by disruption of the peptide's structure. Thus the C-terminal phenylalaninamide is an important factor in this ligand-receptor interaction, and the group itself may interact directly with the receptor.


FEBS Letters ◽  
2002 ◽  
Vol 531 (3) ◽  
pp. 464-468 ◽  
Author(s):  
Daniela Koller ◽  
Walter Born ◽  
Kerstin Leuthäuser ◽  
Beat Flühmann ◽  
R.Anne McKinney ◽  
...  

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