The wewakpeptins, cyclic depsipeptides from a Papua New Guinea collection of the marine cyanobacterium Lyngbya semiplena
The wewakpeptins, cyclic depsipeptides from a Papua New Guinea collection of the marine cyanobacterium Lyngbya semiplena
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DOI：
10.1021/jo0478858
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发表时间：
2005-04-15
影响因子：
3.6
通讯作者：
Gerwick, WH
中科院分区：
文献类型：
--
作者：
Han, BN;Goeger, D;Gerwick, WH
从海洋蓝细菌半脾鞘丝藻（Lyngbya semipelena）中分离到四种新的缩肽。采自巴布亚新几内亚。利用高分辨快原子轰击质谱（HR-FABMS）、1D H-1和C-13 NMR以及2D COSY、HSQC、HSQC-TOCSY和HMBC等波谱技术，对wewakpeptin A-D（1-4）的氨基酸和羟基酸部分结构进行了鉴定。通过多方面方法的组合，包括ESI-MS/MS、HMBC、ROESY和改进的1D HMBC实验，确定了残基的序列。通过手性HPLC和手性GC-MS方法测定每个残基的绝对立体化学。相对于已知的蓝藻肽，wewakpeptin代表了氨基和羟基酸亚基的不寻常排列，并且具有双酯、2，2-二甲基-3-羟基-7-辛炔酸（Dhoya）或2，2-二甲基-3-羟基辛酸（Dhoaa）残基和使人联想到多拉司他汀15的二脯氨酰基。Wewakpeptin A和B是这四种缩肽中最具细胞毒性的，对NCI-H460人肺肿瘤和neuro-2a小鼠神经母细胞瘤细胞系的LC 50约为0.4 μ M。
Four new depsipeptides have been isolated from the marine cyanobacterium Lyngbya semiplena. collected from Papua New Guinea. The amino and hydroxy acid partial structures of wewakpeptins A-D (1-4) were elucidated through extensive spectroscopic techniques, including HR-FABMS, 1D H-1 and C-13 NMR, as well as 2D COSY, HSQC, HSQC-TOCSY, and HMBC spectra. The sequence of the residues was determined through a combination of multifaceted approaches including ESI-MS/MS, HMBC, ROESY, and a modified 1D HMBC experiment. The absolute stereochemistry of each residue was determined by chiral HPLC and chiral GC-MS methods. The wewakpeptins represent an unusual arrangement of amino and hydroxy acid subunits relative to known cyanobacterial peptides and possess a bis-ester, a 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya) or 2,2-dimethyl-3-hydroxyoctanoic acid (Dhoaa) residue, and a diprolyl group reminiscent of dolastatin 15. Wewakpeptin A and B were the most cytotoxic among these four depsipeptides with an LC50 of approximately 0.4 mu M to both the NCI-H460 human lung tumor and the neuro-2a mouse neuroblastoma cell lines.