Kendarimide A, a novel peptide reversing P-glycoprotein-mediated multidrug resistance in tumor cells, from a marine sponge of Haliclona sp.
Kendarimide A, a novel peptide reversing P-glycoprotein-mediated multidrug resistance in tumor cells, from a marine sponge of Haliclona sp.
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DOI：
10.1016/j.tet.2003.07.020
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发表时间：
2004-08-09
期刊：
影响因子：
2.1
通讯作者：
Kobayashi, M
中科院分区：
文献类型：
--
作者：
Aoki, S;Cao, LW;Kobayashi, M
从印尼海绵Haliclona sp.中分离到一种新的肿瘤细胞多药耐药调节剂kendarimide A(1)。化合物1在6um的浓度下逆转P-糖蛋白(P-gp)介导的KB-C2细胞的多药耐药，其化学结构为由N-甲基焦谷氨酸(PyroMeGlu)、N-甲基化八元半胱氨酸(ox-[MeCys-MeCys])和N-甲基氨基酸残基组成的线状肽。通过2D核磁共振和FAB MS分析确定了1的氨基酸序列。通过对1的水解物的Marfey‘s衍生物的高效液相色谱分析和焦甲基谷氨酸残基的合成方法的解释，确定1中除MeCys部分外的氨基酸残基的绝对构型分别为L构型。(C)2004爱思唯尔有限公司。保留所有权利。
A novel modulator of multidrug resistance (MDR) in tumor cells, kendarimide A (1), was isolated from an Indonesian marine sponge of Haliclona sp. Compound 1 reversed MDR in KB-C2 cells mediated by P-glycoprotein (P-gp) at a 6 muM concentration, and the chemical structure of 1 was characterized to be a linear peptide composed of N-methylpyroglutamic acid (pyroMeGlu), N-methylated eight-membered cysteinyl-cysteine (ox-[MeCys-MeCys]) together with many N-methyl amino acid residues. The amino acid sequence of 1 was determined by 2D NMR and FAB MS analysis. The absolute configuration of the amino acid residues in 1 except for the MeCys part was determined to be L-form respectively, based on interpretation of the HPLC analysis of Marfey's derivatives of the hydrolysates of 1 and the synthetic method for the pyroMeGlu residue. (C) 2004 Elsevier Ltd. All rights reserved.