Synthesis and biological activity of highly potent heptapeptide analogs of somatostatin with C-terminal modifications.
OBJECTIVE
Structure-activity relationship studies of a series of new heptapeptide analogs of somatostatin with C-terminal modifications were performed.


METHODS
New somatostatin analogs were synthesized by solid-phase method. The suppression of the release of growth hormone by the new analogs was assayed in vivo in rats, and the duration of action was investigated using growth hormone time-course assay. Growth hormone concentration in plasma samples was determined by RIA.


RESULTS
The growth hormone release inhibitory activity of the new analogs was up to 50 times greater than that of somatostatin. Hydrophilic substitutions at the C-terminus seemed to be advantageous for potency. The most potent analog of the series, D-Phe-c[Cys-Phe-D-Trp-Lys-Thr-Cys]-NH-CH2-CH2-OH showed the most prolonged activity by inhibiting the release of growth hormone for at least 3 h. The analogs containing D-Phe or D-Tyr at the N-terminus were almost equipotent, which proves that the exocyclic N-terminal residue is not involved directly in the receptor recognition.


CONCLUSIONS
New heptapeptide analogs of somatostatin with C-terminal modifications were more potent and longer acting than the native hormone.
Janecka
A
A
Department of General Chemistry, Institute of Physiology, Medical University of Lodz, 90-131 Lozd, Poland. ajanecka@csk.amlodz.pl
Zubrzycka
M
M
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000097:blood; D008297:Male; D008968:Molecular Conformation; D009994:Osmolar Concentration; D051381:Rats; D020318:Rats, Long-Evans; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D013004:Somatostatin; D013006:Growth Hormone