Analogues of Human Calcitonin - II. Influence of Modifications in Amino Acid Positions 1, 8 and 22 on Hypocalcemic Activity in the Rat

Abstract

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 analogue [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.

Abbreviations

HCT: human calcitonin (calcitonin M); SCT₁: salmon calcitonin (major fraction); SCT₂, SCT₃: isohormones of SCT₁(minor fractions); ECT: eel calcitonin; PCT: porcine calcitonin; OCT: ovine calcitonin; Bmp: β-Mercaptopropionic acid (= deamino cysteine); Amino acids are abbreviated according to IUPA-IUB Commission on Biochemical Nomenclature. Biochem. J. 126, 773 (1972)

Key words

Analogues of Human Calcitonin - Salmon Calcitonin and Isohormones - Hypocalcemic Potency - Duration of Action