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RA‐XXV and RA‐XXVI, Bicyclic Hexapeptides from Rubia cordifolia L.: Structure, Synthesis, and Conformation
Author(s) -
Hitotsuyanagi Yukio,
Hirai Masahito,
Odagiri Masumi,
Komine Miho,
Hasuda Tomoyo,
Fukaya Haruhiko,
Takeya Koichi
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201801466
Subject(s) - stereochemistry , chemistry , bicyclic molecule
Abstract Two RA‐series bicyclic hexapeptides, RA‐XXV ( 4 ) and RA‐XXVI ( 5 ), which have no N ‐methyl group at Tyr‐5, were isolated from the roots of Rubia cordifolia L. Their amino acid compositions and sequences were determined by interpretation of MS, and 1D and 2D NMR data and their relative structures were elucidated by XRD analysis of 4 and RA‐XXVI acetate ( 6 ). The absolute stereochemistry of 4 was established by the total synthesis of 4 , and that of 5 , by the chemical correlation with 4 . Peptides 4 and 5 exhibited cytotoxicity toward human promyelocytic leukemia HL‐60 (IC 50 =0.062 and 0.066 μ m , respectively) and human colonic carcinoma HCT‐116 (IC 50 =0.028 and 0.051 μ m , respectively) cell lines. Analysis of the conformational structures of 4 and 6 in the crystalline state and those of 4 and 5 in solution revealed that the N ‐methyl group at Tyr‐5 functions to make this series of peptides preferentially adopt the active conformation.