MACROMOLECULAR PRODRUGS OF 5-FLUOROURACIL .1. SYNTHESIS AND HYDROLYTIC STABILITY

The hydroxyl groups of poly(ethylene glycol), dextran and poly[N-5-(2-hydroxy-ethyl)-L-glutamine] were activated using the 4-nitrophenyl chloroformate method. The resulting phenyl carbonate groups reacted quantitatively with the primary amine groups of oligopeptides with 2-(5-fluorouracil-1-yl) glycine ethyl ester moiety as C-terminus. Following this procedure, 5-fluorouracil-polymer conjugates with peptide chains of different amino acid sequences and configurations were synthesized. The conjugates showed a good hydrolytic stability in buffer solutions of pH 7.4 and 5.5, as well as in calf serum, which indicated good stability of the polymer-drug linkage in the blood.