Prodn. of conformation-stabilised calcitonin derivs. having increased activity

摘要

Prodn. of conformation-stabilised calcitonin analogues (I) having increased hypocalcaemic activity comprises solid phase synthesis on p-methyl-benzhydrylamine resin, combined with a method for 'side chain to side chain' cyclisation of a human calcitonin (h-Ct) analogue. In (I), the aminoacid residue 17 of natural h-Ct is replaced by Asp and the aminoacid residue 21 of natural h-Ct is replaced by Lys and the side chains of these introduced aminoacids are bonded covalently, forming a lactam bridge, to give a cyclo<17.21>-Asp<17>,Lys<21>-hCt with 10-20 fold higher hypocalcaemic activity in mice in vivo, compared with hCt of natural origin.