Archna Mathur

Octapeptide Analogs of Somatostatin Containing α,α-Dialkylated Amino Acids with Potent Anticancer Activity

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-Phe1-Cys2-Tyr3-d-Trp4-Orn5-Xxx6-Pen7-Thr8-NH2 where Xxx=α-Aminoisobutyric acid (Aib), Diethyl glycine (Deg), 1-Aminocyclopentane carboxylic acid (Ac5c), and, d-Phe1-Cys2-Tyr3-d-Trp4-Lys5-Ac5c6-Pen7-Thr8-NH2 (disulphide bond between Cys2 and Pen7 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.

Furanoid Sugar Amino Acids in Design of Analogs of VIP Receptor Binding Inhibitor

Introduction The octapeptide sequence Leu1-Met2-Tyr3-Pro4-Thr5-Tyr6-Leu7-Lys8-OH (1) is reported to be a receptor binding inhibitor of vasoactive intestinal peptide. The anticancer activity of octapeptide 1 in combination with other neuropeptide analogs has been reported [1]. Here we report the peptidomimetic analogs of octapeptide 1 by incorporating furanoid sugar amino acids 2-4. We replaced either Tyr-Pro (analogs 5 and 5a) or Pro-Thr (analogs 6, 6a and 7) in the sequence by furanoid sugar amino acids as depicted in the following figure. In independent studies in the laboratory, the truncated pentapeptide sequence, Met-Pro-Thr-Tyr-Leu-OH, derived from octapeptide 1, was also found to be as active as 1. We also synthesized analogs to this pentapeptide by replacing its Pro-Thr dipeptide segment with sugar amino acids 2 and 3 to get the peptides 8 and 9, respectively.