Synthesis and biological activity of C-terminally truncated fragments of human-.alpha.-calcitonin gene-related peptide

1993 ◽  
Vol 36 (17) ◽  
pp. 2536-2541 ◽  
Author(s):  
D. David Smith ◽  
Jianzhong Li ◽  
Qiming Wang ◽  
Richard F. Murphy ◽  
Thomas E. Adrian ◽  
...  
Keyword(s):  
Biological Activity ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

Biological activity of N-terminal fragments of calcitonin gene-related peptide

1990 ◽  
Vol 179 (1-2) ◽  
pp. 217-219 ◽  
Author(s):  
Carlo Alberto Maggi ◽  
Paolo Rovero ◽  
Sandro Giuliani ◽  
Stefano Evangelista ◽  
Domenico Regoli ◽  
...  
Keyword(s):  
Biological Activity ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Structure-activity relationship of human calcitonin-gene-related peptide

1990 ◽  
Vol 269 (3) ◽  
pp. 775-780 ◽  
Author(s):  
M Zaidi ◽  
S D Brain ◽  
J R Tippins ◽  
V Di Marzo ◽  
B S Moonga ◽  
...  
Keyword(s):  
Blood Flow ◽  
Biological Activity ◽  
Bone Resorption ◽  
Structural Similarity ◽  
Calcitonin Gene Related Peptide ◽  
Human Calcitonin ◽  
Oedema Formation ◽  
Rabbit Skin ◽  
Related Peptide ◽  
Calcitonin Gene

The calcitonin-calcitonin-gene-related peptide (CGRP) gene complex encodes a small family of peptides: calcitonin, CGRP and katacalcin. Calcitonin is a circulating hormone that prevents skeletal breakdown by inhibiting the resorption of bone by osteoclasts. CGRP, a potent vasodilator, is involved in normal regulation of blood flow. The calcitonins structurally resemble the CGRP peptides, and both are known to cross-react at each others' receptors. The present study was undertaken to examine the structural prerequisites for biological activity of the intact CGRP molecule. We therefore prepared eight chymotryptic and tryptic fragments of CGRP and synthesized its acetylated and S-carboxyamidomethylcysteinyl analogues. The analogues were purified by h.p.l.c. and their structures were confirmed by fast-atom bombardment mass spectrometry. We have examined the effects of structurally modified analogues and fragments of human CGRP in a calcitonin-receptor-mediated assay, the osteoclast bone resorption assay, and in one or two CGRP-receptor-mediated assays, the rabbit skin blood flow assay and the oedema formation assay. The results showed that (1) in the osteoclast bone resorption assay, both CGRP peptides, alpha and beta, were equipotent, and were both at least 1000-fold were both approx. 1000-fold more potent than salmon calcitonin; human calcitonin had no effect; (3) the bis- and N-acetylated CGRP analogues retained reduced levels of biological activity in all assays, whereas S-carboxyamidomethylcysteinyl-human CGRP was without activity; and (4) all tryptic and chymotryptic fragments of CGRP were without biological activity, with the exception of hCGRP-(Ala1-Lys35): this fragment had much reduced activity compared with the intact peptide in inhibiting osteoclastic bone resorption and increasing blood flow in the rabbit skin. The results suggest that: (1) calcitonin and CGRP act at distinct receptors to mediate different physiological effects; (2) minor amino acid substitutions, as between the alpha and beta forms of CGRP (these two forms have 94% structural similarity) do not result in differences in biological activity; (3) the intact peptide is required for full biological activity of the CGRP molecule, and even the loss of two amino acids at the C-terminus of the molecule results in a marked decrease in activity; (4) the disulphide bridge appears to play an important role in the interaction of the intact CGRP molecule with its receptor; and (5) the C-terminal region is probably necessary for the peptide to assume the right conformation in the interaction with the receptor.

scholarly journals On the role of the C-terminus of α-calcitonin-gene-related peptide (αCGRP). The structure of des-phenylalaninamide37-αCGRP and its interaction with the CGRP receptor

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 ◽  
...  
Keyword(s):  
Biological Activity ◽  
Calcitonin Gene Related Peptide ◽  
Full Length ◽  
Receptor Interaction ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
C Terminus ◽  
Calcitonin Gene ◽  
Significant Difference

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.

Monoklonale Antikörper gegen CGRP oder den CGRP-Rezeptor in der Migräneprophylaxe

2020 ◽  
Vol 39 (07/08) ◽  
pp. 490-494
Author(s):  
Borries Kukowski
Keyword(s):  
Monoklonale Antikörper ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene

ZUSAMMENFASSUNGDie Charakterisierung von calcitonin gene-related peptide (CGRP) als Schlüsselmolekül in der Pathophysiologie der Migräne hat nicht nur unser Verständnis der Erkrankung, sondern auch die Entwicklung neuer Therapien vorangetrieben. Seit kurzem steht mit den monoklonalen Antikörpern gegen CGRP oder den CGRP-Rezeptor eine spezifische und hoch selektive Option für die medikamentöse Prophylaxe der episodischen und chronischen Migräne zur Verfügung, die in zahlreichen klinischen Studien ihre Überlegenheit gegenüber Placebo belegt hat. Hier werden Erfahrungen aus dem praktischen Behandlungsalltag zur kurz- und mittelfristigen Wirksamkeit und Verträglichkeit mitgeteilt und weitere Aspekte wie Therapiewechsel bei Non-Response, Verlauf nach Therapieende und die Frage des Wirkungsortes unter Einbeziehung bereits publizierter Daten angesprochen.

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