RA‐XXV and RA‐XXVI, Bicyclic Hexapeptides from Rubia cordifolia L.: Structure, Synthesis, and Conformation. Issue 1 (4th December 2018)

• Record Type: Journal Article
• Authors: Hitotsuyanagi, Yukio; Hirai, Masahito; Odagiri, Masumi; Komine, Miho; Hasuda, Tomoyo; Fukaya, Haruhiko; Takeya, Koichi
• Is Part Of: Chemistry, an Asian journal. Volume 14:Issue 1(2019)
• Page Start: 205
• Page End: 215
• Publication Date: 2018-12-04
• Subjects: conformation -- peptides -- Rubia cordifolia -- structure elucidation -- synthesis; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/asia.201801466
• Languages: English
• ISSNs: 1861-4728

Abstract

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 of4 and RA‐XXVI acetate (6 ). The absolute stereochemistry of4 was established by the total synthesis of4, and that of5, by the chemical correlation with4 . Peptides 4 and5 exhibited cytotoxicity toward human promyelocytic leukemia HL‐60 (IC50 =0.062 and 0.066 μm, respectively) and human colonic carcinoma HCT‐116 (IC50 =0.028 and 0.051 μm, respectively) cell lines. Analysis of the conformational structures of4 and6 in the crystalline state and those of4 and5 in solution revealed that the N ‐methyl group at Tyr‐5 functions to make this series of peptides preferentially adopt the active conformation. Abstract : The eye of Ra : Two RA‐series bicyclic hexapeptides, RA‐XXV and RA‐XXVI, which have no N ‐methyl group at Tyr‐5, were isolated from the roots of Rubia cordifolia L. and their absolute structures were established by synthetic methods. Investigation of their conformational properties and cytotoxic activity revealed that the N ‐methyl group at Tyr‐5 is necessary for this series of peptides to take the active conformation preferentially.