Analogues of human calcitonin. II. Influence of modifications in amino acid positions 1, 8 and 22 on hypocalcemic activity in the rat.
The calcitonin analogues [Val8] -HCT and [Tyr22] -HCT, each with a single modification, and [Val8, Tyr22] -HCT and [Bmp1, Val8] -HCT, with two replaced amino acids were compared with synthetic human calcitonin (HCT) in respect of their hypocalcemic effects in the rat. The introduction of either valine in place of methionine in position 8 or of tyrosine for phenylalanine in position 22 of the HCT molecule yielded analogues 4 to 5 times as potent and nearly twice as long-acting as HCT. The doubly substituted peptide [Val8, Tyr22] -HCT displayed properties closely similar to those of [Val8] -HCT and [Tyr22] -HCT. The analgoue [Bmp1, Val8] -HCT, with a deaminated cysteine residue at the N-terminus, was about 6 times more potent than HCT and slightly longer-acting than [Val8] -HCT.
D000818:Animals; D001681:Biological Assay; D002116:Calcitonin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006996:Hypocalcemia / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship
D002116:Calcitonin