THE BINDING OF 5-FLUOROURACIL TO NATIVE AND MODIFIED HUMAN SERUM-ALBUMIN - UV, CD, AND H-1 AND F-19 NMR INVESTIGATION

5-Fluorouracil (FU) is an important and widely used antineoplastic dru g that is carried in the serum by plasma proteins. Protein binding stu dies of this drug to human serum albumin (HSA) have been carried out b y 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 th at FU has at least one secondary binding site in the coumarin binding area, but does not interact with the benzodiazepine binding area. Bind ing was also investigated by difference H-1 NMR and by measuring the i ncrease in the F-19 NMR signal of FU when bound to HSA. Finally, evide nce was obtained that chemical acetylation of Lys(199) results in a de creased apparent binding affinity constant (nK) for FU. Such a modific ation is induced under physiological conditions by aspirin.