Kendarimide A, a novel peptide reversing P-glycoprotein-mediated multidrug resistance in tumor cells, from a marine sponge of Haliclona sp.

A novel modulator of multidrug resistance (MDR) in tumor cells, kendarimide A (), was isolated from an Indonesian marine sponge of Haliclona sp. Compound reversed MDR in KB-C2 cells mediated by P-glycoprotein (P-gp) at a 6 μM concentration, and the chemical structure of 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 was determined by 2D NMR and FAB MS analysis. The absolute configuration of the amino acid residues in except for the MeCys part was determined to be l-form respectively, based on interpretation of the HPLC analysis of Marfeyʹs derivatives of the hydrolysates of and the synthetic method for the pyroMeGlu residue.