title: RA-dimer B, a New Dimeric RA-series Cyclopeptide Incorporating Two Different Types of Cycloisodityrosine Units, from Rubia cordifolia L.
abstract: RA-dimer B, a new cytotoxic RA-series peptide, was isolated from the roots of Rubia cordifolia L. Its structure was elucidated on the basis of spectroscopic analysis to be a dimeric cyclopeptide composed of deoxybouvardin and allo-RA-V. Those two cyclopeptide units are connected by an ether linkage between the phenolic oxygen atom of deoxybouvardin and the ϵa carbon atom of Tyr-6 of allo-RA-V. RA-dimer B was synthesized by the coupling reaction of deoxybouvardin with the boronic acid derivative of allo-RA-V, and subsequent deprotection, confirming the relative stereochemistry and establishing the absolute configuration of this peptide. RA-dimer B showed cytotoxic activity against human promyelocytic leukaemia HL-60, human colonic carcinoma HCT-116, and human renal cell carcinoma ACHN cells with IC50values of 0.59, 0.54, and 0.74 μm, respectively.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hitotsuyanagi
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Ohata
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fukaya
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Hyun Sun
authors.initials: HS
authors.lastname: Park
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeya
authors.affiliation: Research Center for Medicinal Plant Resources, National Institute of Biomedical Innovation, 1-2 Hachimandai, Tsukuba, Ibaraki, 305-0843, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kawahara
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry / Q000378:metabolism; D045470:Rubia / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010456:Peptides, Cyclic; D010936:Plant Extracts
keywords: configuration determination; cytotoxicity; peptides; structure elucidation; synthesis