Correlation between biological potency and biodegradation of a somatostatin analogue

Abstract

ONE approach to the problem of producing peptide hormones of high activity for clinical application is to synthesise analogues which are less rapidly inactivated¹. In the case of luliberin, it was found that an analogue with an inserted D-amino acid and a blocked C terminal end was 80 times more active than the native peptide in vivo. This correlated well with the decreased lysis of the analogue by neutral endopeptidases². There is at present considerable interest in utilising somatostatin clinically. This use is drastically limited by its very short half life of less than 5 min (ref. 3). Somatostatin inhibits the release of growth hormone, thyrotropin and prolactin from the pituitary, of glucagon and insulin from the pancreas, and also of gastrin^3–5. As a consequence there is considerable incentive to prepare longer acting agonists for use in diabetes, and for treatment of developmental disorders.