Constrained analogues of the calcitonin gene-related peptide.
The calcitonin gene-related peptide, CGRP, has potential medicinal use for instance as a vasodilator or in the regulation of bone metabolism. In this study new analogues of CGRP based on molecular modelling of active fragments were synthesised and tested. The analogues were found to have affinities for the receptor comparable to those seen for native CGRP. Two analogues were found to be agonists. The analogues give an insight to the bioactive conformation of CGRP as they were constrained by disulphide bridges.
Turku Centre for Biotechnology, University of Turku, Finland.
J M
JM
Hakala
T
T
Valo
S
S
Vihavainen
J
J
Hermonen
P
P
Heino
M
M
Halme
A M
AM
Koskinen
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004220:Disulfides / Q000032:analysis; D008168:Lung / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011817:Rabbits; D051381:Rats; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D013329:Structure-Activity Relationship
D004220:Disulfides; D010446:Peptide Fragments; D010455:Peptides; D018015:Receptors, Calcitonin Gene-Related Peptide; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide