In the search for selective and long-acting analogs of somatostatin, nearly 200 compounds were synthesized by solid-phase methods, purified, and tested biologically. Among these octapeptides, some contained N-terminal D-Phe1, Ac-D-Phe1, or AcPhe1 followed by hexapeptide sequences Cys2-Phe3-D-Trp4-Lys5-Thr6-Cys7 or Cys2-Tyr3-D-Trp4-Lys5-Val6-Cys7 and Thr8-NH2 or Trp8-NH2 as C-terminal residues. D-Phe-(Cys-Tyr-D-Trp-Lys-Val-Cys)-Thr-NH2 and D-Phe-(Cys-Tyr-D-Trp-Lys-Val-Cys)-Trp-NH2 were 177 times and 113 time more potent, respectively, than somatostatin in tests for inhibition of growth hormone release. These two octapeptides containing tyrosine and valine in positions 3 and 6, respectively, were more active and more selective than their Phe-3 and Thr-6 counterparts, D-Phe-(Cys-Phe-D-Trp-Lys-Thr-Cys)-Thr-NH2 and D-Phe-(Cys-Phe-D-Trp-Lys-Thr-Cys)-Trp-NH2. D-Phe-(Cys-Tyr-D-Trp-Lys-Val-Cys)-Thr-NH2 was also about 6 times more potent that its L-Trp-4 diastereoisomer. The analogs D-Phe-(Cys-Tyr-D-Trp-Lys-Val-Cys)-Thr-NH2 and D-Phe-(Cys-Tyr-D-Trp-Lys-Val-Cys)-Trp-NH2 showed a prolonged duration of action and were able to inhibit growth hormone release for at least 3 hr. Analogs of both Phe-3/Thr-6 and Tyr-3/Val-6 classes also suppressed the release of insulin and glucagon in rats and pentagastrin-induced secretion of gastric acid in dogs, but their potencies in these tests were much smaller than the growth-hormone-release inhibitory activity. Some of these analogs possessed antitumor activities as shown by the inhibition of growth of animal models of prostate, mammary, and ductal pancreatic tumors.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 1986|
ASJC Scopus subject areas