RA-XXV and RA-XXVI, Bicyclic Hexapeptides from Rubia cordifolia L.: Structure, Synthesis, and Conformation
RA-XXV and RA-XXVI, Bicyclic Hexapeptides from Rubia cordifolia L.: Structure, Synthesis, and Conformation
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DOI：
10.1002/asia.201801466
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发表时间：
2019-01-04
影响因子：
4.1
通讯作者：
Takeya, Koichi
中科院分区：
文献类型：
--
作者：
Hitotsuyanagi, Yukio;Hirai, Masahito;Takeya, Koichi
从Rubia cordifolia L.的根中分离到两个ra -系列双环六肽，RA-XXV(4)和RA-XXVI(5)，它们在tyr5上没有n -甲基。通过质谱分析确定了它们的氨基酸组成和序列，并通过XRD分析了4和RA-XXVI乙酸酯的1D和2D NMR数据和它们的相关结构(6)。4的绝对立体化学是通过4的全合成来建立的，5的绝对立体化学是通过与4的化学相关来建立的。肽4和肽5对人早髓细胞白血病HL-60 （IC50分别为0.062和0.066 μ m）和人结肠癌HCT-116 （IC50分别为0.028和0.051 μ m）细胞系具有细胞毒性。对4和6在结晶状态和4和5在溶液状态下的构象结构分析表明，tyr1 -5上的n -甲基使该系列肽优先采用活性构象。
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 (IC50=0.062 and 0.066 mu m, respectively) and human colonic carcinoma HCT-116 (IC50=0.028 and 0.051 mu 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.