Protein-binding patterns of the antitumor antibiotic cryptophycin 52 as measured with a two-phase partitioning system.
Exposure of murine leukemia L1210 cells to the antitumor antibiotic cryptophycin 52 (C52) resulted in a rapid and dose-dependent increase in cell-surface hydrophobicity, as measured with a two-phase partitioning system. This effect was not observed with inactive drug analogs that lacked an epoxy residue. While the C52 has distinctly hydrophobic properties, the drug does not uniformly bind to all proteins. Affinity for human high- and low-density lipoprotein and albumin was demonstrated, but the drug binds only to the albumin fraction of mouse plasma, in spite of the high HDL level in the latter species.
Kessel
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Departments of Pharmacology and Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA. dhkessel@med.wayne.edu
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000378:metabolism*; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism; D047630:Depsipeptides; D006801:Humans; D007700:Kinetics; D007769:Lactams / Q000097:blood / Q000378:metabolism*; D007783:Lactones / Q000097:blood / Q000378:metabolism*; D007939:Leukemia L1210 / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D051379:Mice; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D001798:Blood Proteins; D047630:Depsipeptides; D007769:Lactams; D007783:Lactones; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D012709:Serum Albumin; C114033:cryptophycin 52