We describe the synthesis and anticancer activities of octapeptide analogs of somatostatin incorporating α,α-dialkylated amino
acids. The designed analogs of somatostatin are:
d-Phe
1-Cys
2-Tyr
3-
d-Trp
4-Orn
5-Xxx
6-Pen
7-Thr
8-NH
2 where Xxx=α-Aminoisobutyric acid (Aib), Diethyl glycine (Deg), 1-Aminocyclopentane carboxylic acid (Ac5c), and,
d-Phe
1-Cys
2-Tyr
3-
d-Trp
4-Lys
5-Ac5c
6-Pen
7-Thr
8-NH
2 (disulphide bond between Cys
2 and Pen
7 in all analogs). The conformational studies two of the designed analogs were carried out by NMR techniques and the experimental
results suggest a β-turn structure for one of the designed analog.
In vivo tumor regression study of two designed analogs on human primary colon tumor xenografts in nude mice demonstrates the anticancer
potential of the synthesized analogs.
Keywords Somatostatin - α,α-dialkylated amino acids - anticancer peptides