The total synthesis and functional evaluation of fourteen stereoisomers of yaku'amide B. The importance of stereochemistry for hydrophobicity and cytotoxicity. Issue 18 (22nd April 2016)

• Record Type: Journal Article
• Authors: Mutoh, Hiroyuki; Sesoko, Yusuke; Kuranaga, Takefumi; Itoh, Hiroaki; Inoue, Masayuki
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 18(2016)
• Page Start: 4199
• Page End: 4204
• Publication Date: 2016-04-22
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c6ob00640j
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Yaku'amide B is a highly unsaturated linear tridecapeptide and an extremely potent cytotoxin. Abstract : Yaku'amide B is a highly unsaturated linear tridecapeptide and an extremely potent cytotoxin. Herein, we describe the synthesis of fourteen new stereoisomers of yaku'amide B using a unified assembly strategy. The hydrophobicities and cytotoxicities of these analogues were analyzed, along with those of four previously prepared isomers. Although all of the analogues share a common planar structure, their log D values varied significantly (3.39–5.32), presumably reflecting their distinct three-dimensional shapes. Subnanomolar-level cytotoxicity was observed for the natural yaku'amide B and its epimer of the N-terminal acyl group, whereas the other sixteen isomers exhibited 13- to 1200-fold weaker activities than that of the natural isomer. These data indicated the importance of the overall stereostructure of the 13-mer sequence of yaku'amide B for exerting its potent toxicity.