Mechanism of action of didemnin B, a depsipeptide from the sea.
With the brush border membrane vesicles prepared from the rat kidney cortex, didemnin B and its parent compound, didemnin A function neither as a K+-specific ionophore nor as an ionophore for Na+ ions while other depsipeptide antibiotics such as valinomycin and gramicidin promote transmembrane movement of K+ and Na+ ions, respectively. Didemnin B inhibits protein synthesis and DNA synthesis much more than RNA synthesis and is in general more potent than didemnin A. Time course studies reveal that the action of didemnin B is rapid and cannot be reversed after 2 h in contact with the cells. The inhibition of protein synthesis is almost superimposable to that of L1210 cells growth. DNA synthesis is also markedly inhibited. These results collectively suggest that didemnin B acts differently, at least in part, from other depsipeptide antibiotics and its biological effect is primarily mediated through its inhibition of protein synthesis and to a lesser extent its inhibition of DNA synthesis.
D000818:Animals; D000903:Antibiotics, Antineoplastic; D001693:Biological Transport, Active / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D047630:Depsipeptides; D066298:In Vitro Techniques; D007476:Ionophores; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010456:Peptides, Cyclic / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis; D051381:Rats; D012964:Sodium / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D047630:Depsipeptides; D007476:Ionophores; D009363:Neoplasm Proteins; D010456:Peptides, Cyclic; D012334:RNA, Neoplasm; C030051:didemnins; D012964:Sodium; D011188:Potassium