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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Authors: | Shunji Aoki Kouhei Matsui Shin-ichi Akiyama |
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Institution: | a Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan b Research and Development Centre for Oceanology, LIPI, JL. Pasir Putih I, Ancol Timur, Jakarta 11048, Indonesia c Department of Cancer Chemotherapy, Institute for Cancer Research, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan |
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Abstract: | 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 μM 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. |
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Keywords: | Multidrug resistance Marine sponge Haliclona sp Kendarimide A N-methyl amino acid |
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