Increase in Amidase Activity of Trypsin by Complexation with Block Ionomers Having Poly(carboxylate) Block

摘要

The exocrine pancreas synthesizes, stores and secretes hydrolytic enzymes required for the intestinal digestion of food. Among these enzymes is the family of serine proteinases including trypsin, chymotrypsin, elastase and kallikrein. The members of this family are probably related by evolution and come from a common ancesyral proteinase, and have retained a similar structure, size and function. As is well known, the Asp, His and Ser triad as common catalytic sites play an important role in the catalytic reaction of the enzymatic function of this family. On the other hand, in the field of polymer science, the complexes of bioactive compounds, such as enzymes and DNA, with synthetic polymers have been widely investigated. Particularly, the water-soluble complexes of bioactive compounds with block ionomers have recently received considerable attention Since these complexes formed a micelle-like structure, the utilities as a vehicle for bioactive compounds in the drug delivery field are expected. We have investigated the complexes of charged enzymes with block ionomers In such studies, we have recently found that the amidase activity of bovine pancreas trypsin, which is the family of serine proteinase, was facilitated through the formation of water-soluble complexes with poly(ethylene glycol)-block-poly(?,β-aspartic acid) (PEG-PAA) This facilitation effect was due to the stabilization of the catalytic triad, the Asp-His-Ser residues, by the carboxylate group of PEG-PAA. If the carboxylate group is important for facilitation of the amidase activity, the same effect is also expected for the other block ionomers having polycarboxylate blocks.