Abstract
The semitelechelic poly[N-(2-hydroxypropyl)methacrylamide] [poly(HPMA)] with a carboxyl end group was prepared with 3-mercaptopropionic acid as a chain transfer agent. Bovine seminal ribonuclease (BSR) and α-chymotrypsin (ChT) were modified with various molecular weights of active poly(HPMA) succinimidyl ester by the reaction with the amino groups of the respective enzyme. The modification of ChT did not significantly change the activity or the substrate specificity of the conjugates towards low-molecular-weight tripeptidic substrates. However, modified ChT activity towards the corresponding poly(ethylene glycol)-based synthetic substrate was significant. The activity decreased as a result of the elevated steric hindrance to the active site of the polymer-modified enzyme. Similarly, the ChT conjugates completely lost their proteolytic activity toward native bovine serum albumin. The autolytic stability of ChT conjugates was improved and the proteolytic stability of the ChT and BSR conjugates substantially increased compared with the free enzymes. The modification of ChT with poly(HPMA) significantly decreased the immunogenicity of ChT conjugates depending on the molecular weight of the poly(HPMA) and the degree of enzyme substitution.
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