Design of Proteinase–Catalyzed Synthesis of Oligopeptides in an Aqueous–Organic Biphasic System

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Abstract

Thermolysin–catalyzed condensation of N – (benzylxycarbyl) – glycyl – glycyl – L –phenylalanyl–L–leucine ethyl ester (Z–Gly–GlyPheLeuOEt), the precursor of the des–Tyr1–leucine enkephalin from N–(benzyl–oxycarbonyl)–glycyl–glycine (Z–GlyGly) and L–phenylalanyl–L–leucine ethyl ester (PheLeuOEt) was elucidated as a model reaction for the enzymatic synthesis of oligopeptides with many side reactions. In buffer solution, the yield of Z–GlyGly–PheLeuOEt was extremely low with considerable by–products. A large increase in both yield and purity became possible in the aqueous–organic biphasic system by the systematic selection of experimental conditions.

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Nakanishi, K., Kimura, Y. & Matsuno, R. Design of Proteinase–Catalyzed Synthesis of Oligopeptides in an Aqueous–Organic Biphasic System. Nat Biotechnol 4, 452–454 (1986) doi:10.1038/nbt0586-452

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