Synthesis, conformational analysis and bioactivity of Lan-7, a lanthionine analog of TT-232. |
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Authors: | H Li X Jiang S B Howell M Goodman |
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Affiliation: | Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla 92093-0343, USA. |
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Abstract: | A sandostatin analog, TT-232 (D-Phe-c[Cys-Tyr-D-Trp-Lys-Cys]-Thr-NH2), 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 TT-232. |
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