Furanoid sugar amino acids as dipeptide mimics in design of analogs of vasoactive intestinal peptide receptor binding inhibitor

Abstract: In this study we describe the development of peptidomimetic analogs of the potent vasoactive intestinal peptide receptor binding inhibitor, Leu¹ ‐Met² ‐Tyr³ ‐Pro⁴ ‐Thr⁵ ‐Tyr⁶ ‐Leu⁷ ‐Lys⁸ ‐OH 1, by incorporating furanoid sugar amino acids (SAAs) 2‐4 into the molecule. The furanoid SAAs 2‐4 were used as dipeptide isosteres to replace Tyr³ ‐Pro⁴ or Pro⁴ ‐Thr⁵ in sequence 1 . The resulting analogs 5 ‐ 9 were tested for their anti‐cancer activities in vitro, following the standard MTT assay on a panel of human cancer cell lines. One of the potent analogs, 6a was tested in vivo for tumor regression on primary colon tumor xenografted nude mice. Our experimental results suggest that many of these analogs show either retention or enhancement of biological activity.