Structure-activity relationship of calcitonin gene related peptide.
Chicken, human(alpha) CGRPs and their analogues were synthesized to investigate the relationship between structure and serum calcium and phosphate lowering effects. The native hormones contain 37 amino acid residues with only four positions (3, 14, 15 and 23) that differ. Chicken CGRP exhibits stronger and longer lasting activities than the human hormone. A chicken CGRP analogue with replacement of Asp at position 14 by Gly (as in human CGRP) showed great reduction of activity. The converse replacement of Gly at position 14 by Asp in human CGRP enhanced this analogue activity. Among the synthetic analogues, des-1-Ala-des-alpha-amino chicken CGRP, exhibited the most potent and long lasting biological activity.
Morita
K
K
Research Laboratory, Toyo Jozo Co., Ltd., Shizuoka, Japan.
Kato
I
I
Uzawa
T
T
Hori
M
M
Noda
T
T
D000595:Amino Acid Sequence; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002645:Chickens; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010710:Phosphates / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship
D010710:Phosphates; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium