Abstract
A systematic study of enzymatic peptide synthesis in heterogeneous substrate mixtures was carried out, with the aim of establishing the preparative scope of this methodology. Semiliquid eutectics were obtained with various combinations of neutral, acidic, and basic amino acid derivatives, in the presence or absence of adjuvants. A range of serine cysteine, and metalloproteases readily catalyzed the formation of the required dipeptides under these conditions. The synthetic usefulness of the approach was demonstrated by the sequential and convergent synthesis of derivatives of a number of bioactive di-, tri-, and pentapeptides, including aspartame, sweet lysine peptide, kyotorphin amide, ACE-inhibiting and -immunoactive tripeptides, and Leu-enkephalin amide, with overallyields of 21% to 84% and productivities of 0.13 to 0.75 g/g being obtained. (c) 1994 John Wiley & Sons, Inc.
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