Studies On Synthesisis Of Macromolecular Prodrugs Of5-fluorouracil And Their Interactions With Bovin Serum Albumin

Aiming at improving the disadvantage of5-Fu which lacks of the tissue selectivity,has short organisms half-life and low bioavailability, has strong side effects, thisresearch has proposed grafting5-fluorouracil-1-yl acetic acid（5-FuAc） onto chitosanand chitosan oligosaccharide, obtained the macromolecular prodrugs of5-fluorouracil.Polymeric prodrugs of5-fluorouracil can reduce its toxicity, increase duration ofantitumor activity and additionally, an affinity for tumor cells.Then, this paper investigates the interaction between BSA and modified medicinesincluding the action mechanism, action zone, acting force, binding sites throughusing several spectroscopic techniques. The result of researches is helpful tounderstand the absorption, distribution, excretion and pharmacological ac-tivity inhuman body as well as has an important and guiding significance to know the impactdrugs on structure and function of protein further and to research and develop newmedicine better.The main research results and conclusions are as follows:1.5-fluorouracil-1-yl acetic acid（5-FuAc） by the ester bond is grafted-OH of CSand COS, made sure that5-Fu grafts onto the polymers. It used the IR and otherspectrums to confirm structure of prodrugs. Then, The drugloaded rate was6.88%and4.12%respectively.2.The interaction of CS-5-Fu with BSA have been studied by FS technique incombination with UV-Vis absorption spectroscopy, CD spectroscopy under thesimulative physiologyical conditions. The results showed that the quenching was astatic quenching procedure. The binding constants were calculated to be7.5523,4.0985,1.3086×10³L·mol-1at290,300, and310K. According to the Van’t Hoffequation, the parameters indicated that CS-5-Fu interacted with BSA mainly throughhydrophobic forces and electrostatic forces. The entropy increase and the free energyreducing in this process proved it’s a spontaneous procedure. The binding distancewas calculated to be1.76nm according to the theory of F rster’s non-radiation energy transfer. The displacement experiments pointed out that CS-5-Fu could bindto the SiteⅠ of BSA. Alteration ofstereostructure in the presence of CS-5-Fu wasconfirmed by CD spectroscopy and synchronous fluorescence spectroscopy.3. To study the interaction mechanism of BSA with COS-5-Fu under the samemeyhod. The results showed that the quenching of BSA fluorescence by COS-5-Fuwas a static quenching procedure. Calculated the binding constants was2.4932,2.0206,1.2362×10³L·mol^-1at290,300, and310K. According to the Van’t Hoffequation, the parameters indicated as same as CS-5-Fu interacted with BSA. Thebinding distance was calculated to be1.84nm according to the theory of F rster’snon-radiation energy transfer. The displacement experiments suggested thatCOS-5-Fu could bind to the Site Ⅰ of BSA.Alteration of stereostructure in thepresence of COS-5-Fu was confirmed by CD spectroscopy and synchronousfluorescence spectroscopy.