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 -NH 2 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 -NH 2 groups, which were reacted with benzoyl chloride to obtain a model prodrug system. The products synthesized were characterized by IR, 1 H-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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.