Antitumor drug-protein interactions. Binding of 1-beta-D-arabinofuranosyl cytosine to albumin and chemically modified albumin.
Equilibrium dialysis measurements were carried out to study the binding of 1-beta-D-arabinofuranosyl cytosine (ara-C) to human and bovine serum albumin (HSA, BSA) and to chemically modified albumin. The binding of 4-phenylbutyric acid to HSA was studied, too. Binding data were presented as Scatchard plots. There are two types of binding sites of different affinity for ara-C both on HSA and BSA. The relatively small value of affinity constant indicates that the pharmacological properties of ara-C might not be influenced very strongly by the HSA interaction or by competitive binding of other drugs. Selective chemical modifications of HSA with diethylpyrocarbonate (DEP) or o-nitrophenylsulfenyl chloride (NPS-Cl) reduce significantly the affinity of the strong binding area. On the other hand, the attachment of poly-alpha-L-glutamyl or poly-DL-alanyl side-chains to BSA increase the number of the strong and secondary binding sites and also the affinity at the first group of sites. Experimental results suggest a correlation between the binding affinity and therapeutic efficacy of various cytotoxic drug-protein complexes.
D000818:Animals; D002417:Cattle; D003561:Cytarabine / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism
D012709:Serum Albumin; D003561:Cytarabine; D012710:Serum Albumin, Bovine