Synthesis, conformational analysis and bioactivity of Lan-7, a lanthionine analog of TT-232

✍ Scribed by Haitao Li; Xiaohui Jiang; Stephen B. Howell; Murray Goodman

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 497 KB
• Volume: 6
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/(sici)1099-1387(200001)6:1<26::aid-psc231>3.0.co;2-6

✦ Synopsis

A sandostatin analog, TT-232 (D-Phe-c[Cys-Tyr-D-Trp-Lys-Cys]-Thr-NH 2 ), exhibits strong antitumor effects both in vitro and in vivo. In order to study the structure -activity relationships of TT-232, we designed and synthesized an analog of TT-232, namely Lan-7, in which the disulfide bridge is replaced by a lanthionine monosulfide bridge. Conformational analysis by NMR spectroscopy and computer simulations revealed that Lan-7 and TT-232 adopt very similar conformations in solution, which are quite different from the preferred conformations of sandostatin. Lan-7 has significant growth inhibition effects on a number of human tumor cell lines. It can also induce apoptosis in human ovarian carcinoma 2008 cells. At the same time, Lan-7 produced no toxicity to normal human hematopoietic progenitor cells. All of these results indicate that the modification we made does not alter the anti-tumor activity of