Poly(ethylene glycol)s containing enzymatically degradable bonds

Abstract

AbstractThe possibility to use poly(ethylene glycol) (PEG) as a synthetic, water‐soluble polymeric carrier of biologically active compounds was investigated. The relationship between structure of oligopeptide (amino acid)‐PEG conjugates and their hydrolysis catalyzed by chymotrypsin was studied. Two types of derivatives were synthesized: Derivatives of PEG 2000, containing an oligopeptide sequence terminating in p‐nitroaniline (drug model) and higher molecular weight derivatives of PEG 2000 containing in the main chain enzymatically and hydrolytically degradable bonds. The rates of chymotrypsin catalyzed release of p‐nitroaniline at pH 8,0 and 25°C were determined over a range of substrate concentrations to derive values for kcat and KM. The influence of the length and detailed structure of the oligopeptide sequence on the rate of hydrolysis was demonstrated. Comparison with copolymers of N‐(2‐hydroxypropyl)methacrylamide and poly(maleic anhydride‐co‐vinylpyrrolidone) showed that the sterical hindrance of the formation of the enzyme‐substrate complex is much less pronounced in the PEG‐oligopeptide conjugates. The latter conclusion is also valid in the case of cleavage of PEG derivatives which contain enzymatically degradable bonds in the main chain. The incorporation of a single amino acid residue (phenylalanine) into the main PEG chain is sufficient to make the polymer susceptible to chymotrypsin catalyzed hydrolysis.