Association of the radiosensitizers metronidazole and misonidazole (RO-07-0582) with bovine serum albumin. Effect of urea and ionic strength.
The stability of association of nitroimidazole radiosensitizers (metronidazole and misonidazole) with bovine serum albumin (BSA) was examined in aqueous solutions by 1H n.m.r. spectroscopy in the presence of urea (0-8M) as denaturant, or high salt concentration (NaCl0-5M). A broadening of n.m.r. lines of the two radiosensitizers observed in the presence of BSA disappeared with increasing urea concentration. An especially large narrowing effect was observed for the lines attributed to the methylene group near to the hydroxyl in the side chain of misonidazole. The results suggest a release of both radiosensitizers from their binding sites on unfolding by urea of the polypeptide chain of BSA. The increase of ionic strength I caused a monotonic enhancement of broadening by BSA of the metronidazole lines. For misonidazole, the enhancement of broadening was observed at values of I greater than 1, but at low (less than 1 M) concentrations of NaCl the broadening disappeared. Thus, the results obtained in the systems with salt reflect quantitative changes in hydrophobic and hydrogen-bonded contributions to binding of aliphatic moieties of radiosensitizers to BSA.
D009682:Magnetic Resonance Spectroscopy; D008795:Metronidazole; D008920:Misonidazole; D009593:Nitroimidazoles; D009994:Osmolar Concentration; D011485:Protein Binding; D011838:Radiation-Sensitizing Agents; D012710:Serum Albumin, Bovine; D014508:Urea
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008795:Metronidazole; D012710:Serum Albumin, Bovine; D008920:Misonidazole; D014508:Urea