On the role of the C-terminus of alpha-calcitonin-gene-related peptide (alpha CGRP). The structure of des-phenylalaninamide37-alpha CGRP and its interaction with the CGRP receptor.
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.
O'Connell
J P
JP
Celltech Ltd., Slough, Berks, U.K.
Kelly
S M
SM
Raleigh
D P
DP
Hubbard
J A
JA
Price
N C
NC
Dobson
C M
CM
Smith
B J
BJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000577:Amides / Q000737:chemistry*; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002942:Circular Dichroism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D010649:Phenylalanine / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000577:Amides; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D010649:Phenylalanine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide