Structure activity relationship study of cyclic depsipetide callipeltins with anti-HIV activity

2015 Fiscal Year Final Research Report

• Project/Area Number: 25450145
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Yamagata University
• Principal Investigator: Konno Hiroyuki 山形大学, 理工学研究科, 准教授 (50325247)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 環状デプシペプチド / CCR5阻害剤 / 異常アミノ酸 / TAK779 / ペプチド固相合成法 / 蛍光標識化 / 細胞毒性 / HEK/CCR5

Outline of Final Research Achievements

The peptides contained with unusual amino acids show several biological activities, especially anti-HIV activity. We have attempted to synthesize cyclic depsipeptides callipeltins and homopymines with several unusual amino acids. Preparation of unusual amino acids were achieved by stereoselective synthesis in solution phase. Peptide constructions were used by standard Fmoc-solid phase peptide synthesis and cyclization and final deprotection were proceeded smoothly by optimized conditions to give callipeltin B and cyclic fragment of homophymines. We found that purified callipeltin B included the contamination of callipeltins C and H at a ratio of approximately 15%. These results suggested that the cytotoxicity of natural callipeltin B was derived from callipeltins C and H. On the other hand, TAK779 bound with coumarin was attempted for the preparation of new method of evaluation of anti-HIV activities.

Free Research Field

生物有機化学