Department of Chemistry and Biochemistry, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan; Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Bioorg Med Chem. 2018 Jul 30;26(13):3852-3857. doi: 10.1016/j.bmc.2018.06.042. Epub 2018 Jun 30.
Sameuramide A (1), a new cyclic depsipeptide encompassing one each of alanine, N-methyl alanine, N-methyl dehydroalanine, N,O-dimethyl threonine, phenyllactic acid, three β-hydroxy leucines, and two propionates, was isolated from a didemnid ascidian collected at the northern part of Japan. The planar structure was established based on the interpretation of MS and NMR data. The absolute configuration of the subunits was determined by the advanced Marfey's method and the chiral LC-MS analysis. Compound 1 exhibited the activity of maintaining colony formation of murine embryonic stem (mES) cells without leukemia inhibitory factor (LIF). Down regulation of the gene expression of Krüppel-like transcription factor 4 (Klf4) indicated that 1 itself was not able to maintain the undifferentiated state of the mES cells. However, the expression levels of the marker genes (Nestin, T, Sox17) for three germ layers were upregulated in embryoid bodies (EBs) after treatment of 1 together with LIF, suggesting that 1 plays a supportive role for LIF in maintaining the multipotency of mES cells.
从日本北部采集的一种迪斯米尼达鞘氨醇中分离得到了 Sameuramide A（1），这是一种新的环状二肽，包含一个丙氨酸、N-甲基丙氨酸、N-甲基脱氢丙氨酸、N,O-二甲基苏氨酸、苯乳酸、三个β-羟基亮氨酸和两个丙酸盐。基于 MS 和 NMR 数据的解释，确定了平面结构。通过先进的 Marfey 法和手性 LC-MS 分析确定了亚基的绝对构型。化合物 1 表现出维持小鼠胚胎干细胞（mES）细胞集落形成而无需白血病抑制因子（LIF）的活性。Krüppel 样转录因子 4（Klf4）的基因表达下调表明 1 本身不能维持 mES 细胞的未分化状态。然而，在用 1 与 LIF 一起处理后，胚状体（EBs）中三个胚层的标记基因（Nestin、T、Sox17）的表达水平上调，表明 1 在维持 mES 细胞的多能性方面为 LIF 提供支持。
