Macromolecular Prodrugs of 5-Fluorouracil. 1: Synthesis and Hydrolytic Stability

Author:

Nichifor Marieta1,Coessens Veerle1,Schacht Etienne H.1

Affiliation:

1. Department of Organic Chemistry, Biomaterial & Polymer Research Group, University of Gent, Krijgslaan 281 S4 bis, 9000 Gent, Belgium

Abstract

The hydroxyl groups of poly(ethylene glycol), dextran and poly-[N5-(2-hydroxy-ethyl-L-glutamineI 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.

Publisher

SAGE Publications

Subject

Materials Chemistry,Polymers and Plastics,Biomaterials,Bioengineering

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