Conformational requirements for activity of salmon calcitonin.
A series of deletion-substitution analogs of salmon calcitonin (SCT) have been prepared containing combinations of a glycine substitution in position 8 and deletions of serine-2 and tyrosine-22. Biological activity of the analogs with respect to native SCT were determined in the rat hypocalcemic assay and by studying stimulation of cAMP formation and competition for binding of 125I-labeled SCT in T47 D human breast cancer cells. It was found that each of the analogs retained full potency, irrespective of the means of assessment. It is suggested that conservation of the alpha-helical region of SCT, along with the overall tertiary structure, are more important for peptide potency than chain length per se.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001681:Biological Assay; D001943:Breast Neoplasms / Q000201:enzymology; D002116:Calcitonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002460:Cell Line; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced; D051381:Rats; D012474:Salmon; D013329:Structure-Activity Relationship
D002116:Calcitonin; D000262:Adenylyl Cyclases