5-Fluorouracil (FU) is an important and widely used antineoplastic drug that is carried in the serum by plasma proteins. Protein binding studies of this drug to human serum albumin (HSA) have been carried out by several spectroscopic techniques. Difference circular dichroism and UV studies provided information on the class of binding sites involved in the interaction. In particular, displacement experiments showed that FU has at least one secondary binding site in the coumarin binding area, but does not interact with the benzodiazepine binding area. Binding was also investigated by difference H-1 NMR and by measuring the increase in the F-19 NMR signal of FU when bound to HSA. Finally, evidence was obtained that chemical acetylation of Lys(199) results in a decreased apparent binding affinity constant (nK) for FU. Such a modification is induced under physiological conditions by aspirin.
The Binding of 5-Fluorouracil to Native and Modified Human Serum Albumin: UV, CD, and 1H and 19F NMR Investigation
UCCELLO BARRETTA, GLORIA;DI BARI, LORENZO;SALVADORI, PIERO
1995-01-01
Abstract
5-Fluorouracil (FU) is an important and widely used antineoplastic drug that is carried in the serum by plasma proteins. Protein binding studies of this drug to human serum albumin (HSA) have been carried out by several spectroscopic techniques. Difference circular dichroism and UV studies provided information on the class of binding sites involved in the interaction. In particular, displacement experiments showed that FU has at least one secondary binding site in the coumarin binding area, but does not interact with the benzodiazepine binding area. Binding was also investigated by difference H-1 NMR and by measuring the increase in the F-19 NMR signal of FU when bound to HSA. Finally, evidence was obtained that chemical acetylation of Lys(199) results in a decreased apparent binding affinity constant (nK) for FU. Such a modification is induced under physiological conditions by aspirin.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
