| Abstract: | We have synthesized a novel enzymatically degradable prodrug system based on poly(ethylene glycol) (PEG) and tyrosine units by employing a synthetic methodology which eliminated the use of conventional blocking and deblocking methodology used for chemical linkage of drug molecule to the pendant ? NH2 group of amino acid. A diester of PEG (6 kDa) and tyrosine hydrochloride was synthesized by dicyclohexyl carbodiimide (DCC)‐mediated condensation. In the second stage, oligomers were prepared by condensing phenolic ? OH groups of tyrosine in the diester with sebacic acid, using DCC. Finally, the hydrochloride salt of tyrosine in the oligomer was treated with triethylamine to activate ? NH2 groups, which were reacted with benzoyl chloride to obtain a model prodrug system. The products synthesized were characterized by IR, 1H‐NMR, and GPC. The spectral data were in accordance with the proposed structures of products. Chymotrypsin‐catalyzed degradation of the oligomers was characterized by both MW measurements and Ninhydrin assay for free tyrosine. Degradation studies indicated that the rate of main‐chain degradation (ester hydrolysis) is higher than that of the side chain (amide hydrolysis). This new, simple methodology should be useful for conjugating a variety of bioactive molecules to enzymatically degradable PEG–amino acid based polymers. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2108–2118, 2002 |
