Tyrosylated analogues of somatostatin.

The total synthesis of [tyr1]-, [tyr6]-, E1Tyr7], [d-tyr8]-, [tyr11]-,and [tyr1,D-Trp8]somatostatin is described. The biological potencies of these analogues in vitro (inhibition of spontaneous secretion of radioimmunoassayable growth hormone by cultured rat anterior pituitary cells) as compared with that of somatostatin (100) were found to be 116, 29, 108, 10, 65, and 400, respectively; in vivo, in the rat, these peptides were assayed for their ability to inhibit the spontaneous release of insulin and glucagon. No statistically significant discrepancies were observed in the potency values obtained in vitro and in vivo further indicating similarities of specificities and sensitivities of the pituitary and pancreatotropic receptors.