Apratoxin E, a cytotoxic peptolide from a guamanian collection of the marine cyanobacterium Lyngbya bouillonii
Apratoxin E, a cytotoxic peptolide from a guamanian collection of the marine cyanobacterium Lyngbya bouillonii
复制标题
DOI：
10.1021/np700717s
复制
发表时间：
2008-06-01
影响因子：
5.1
通讯作者：
Luesch, Hendrik
中科院分区：
文献类型：
--
作者：
Matthew, Susan;Schupp, Peter J.;Luesch, Hendrik
来自关岛的一批海洋蓝细菌布氏鞘囊藻（Lyngbya bouillonii）产生了一种新的肽-聚酮杂合物--阿曲毒素E（1），属于阿曲毒素类细胞毒素。通过核磁共振和质谱分析确定了化合物1的平面结构。通过对酸水解产物的手性HPLC分析，对肽部分中的立体中心进行解析分配。通过比较NMR数据（包括质子-质子耦合常数）与已知类似物的NMR数据，分配聚酮部分的相对构型。Apratoxin E（1）对几种来自结肠、子宫颈和骨的癌细胞系显示出很强的细胞毒性，范围为21 - 72 nM，表明修饰的半胱氨酸残基的α，β-不饱和对Apratoxin活性不是必需的。与黄曲霉毒素A（2）相比，其活性降低了5至15倍，这是由于长链聚酮单元的脱水，这可能影响分子的构象。
A collection of the marine cyanobacterium Lyngbya bouillonii from Guam afforded apratoxin E (1), a new peptide-polyketide hybrid of the apratoxin class of cytotoxins. The planar structure of 1 was elucidated by NMR spectroscopic analysis and mass spectrometry. Configurational assignments of stereocenters in the peptide portion were made by chiral HPLC analysis of the acid hydrolysate. The relative configuration in the polyketide moiety was assigned by comparison of NMR data including proton-proton coupling constants with those of the known analogues. Apratoxin E (1) displayed strong cytotoxicity against several cancer cell lines derived from colon, cervix, and bone, ranging from 21 to 72 nM, suggesting that the alpha,beta-unsaturation of the modified cysteine residue is not essential for apratoxin activity. The 5- to 15-fold reduced activity compared with apratoxin A (2) is attributed to the dehydration in the long-chain polyketide unit, which could affect the conformation of the molecule.