Generation and Application of All Possible Conformations of Cyclic Tryptophan within and beyond Post-translational Modification.

Autor:	Kasahara A; Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan., Yamada R; Faculty of Chemistry and Biochemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan., Hyodo T; Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan., Yamaguchi K; Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan., Otani Y; Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan., Sumimoto S; Faculty of Chemistry and Biochemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan., Okada M; Faculty of Chemistry and Biochemistry, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan., Ohwada T; Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Jazyk:	angličtina
Zdroj:	The Journal of organic chemistry [J Org Chem] 2024 Dec 20. Date of Electronic Publication: 2024 Dec 20.
DOI:	10.1021/acs.joc.4c02532
Abstrakt:	Isoprenylation of the indole C3-position of tryptophan accompanied by cyclization (c-Trp) is one of the most attractive post-translational modifications because of C-C bond formation and drastic conformational alteration. As the modification generates two stereoisomers of the 6/5/5-fused ring system and consequently, a mixture of four possible conformations as considered in proline, it is expected to influence the biological activity in Bacillus quorum sensing pheromone ComX containing the c-Trp residue. In this study, the simultaneous control of the amide cis-trans equilibrium and pyrrolidine ring puckering was achieved by utilizing an N-carbamoylated and α-methylated 6/5/5-fused ring system. Furthermore, the conformationally defined tripeptides containing the c-Trp residue were utilized to examine the relationship between the biological activity and the conformation of the ComX pheromone. Several mimics showed high bioactivity, and more biologically active ComX mimics were created to reinforce the CH-π interaction of the c-Trp and the adjacent aromatic residue.
Databáze:	MEDLINE
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