ENZYMATIC SYNTHESES OF N-PROTECTED LEU-ENKEPHALIN AND SOME OLIGOPEPTIDES IN ORGANIC-SOLVENTS

Enzymatic syntheses of bioacitive pentapeptide, N-protected Leu-enkeph alin and some other oligopeptides in organic solvents were studied. Th e stereoselectivity of the enzymatic reaction was examined by using ra cemic substrates. Different enzymes, solvent systems and protecting gr oups were compared. The importance of the essential water was addresse d. The side chain of tyrosine was not protected during all the enzymat ic reactions. P-DL-AlaOY (P=Z or Boc, Y=H or Me) and P-DL-TyrOEt were coupled with GlyNHNHPh by papain and alpha-chymotrypsin in mixed solve nt or organic solvent to obtain the expected optically pure products P -L-AlaGlyNHNHPh and P-L-TyrGlyNHNHPh respectively in good yield. Two s weetener precursors, ZAspXaaOR (XaaOR=PheOMe or AlaOcHex) were synthes ized by thermolysin in tert-amyl alcohol and some reaction conditions were optimized to get the best yield. Full enzymatic synthesis of N-pr otected Leu-enkephalin ZTyrGlyGlyPheLeuOH was investigated using a-chy motrypsin and thermolysin as catalysts in dichloromethane and tert-amy l alcohol. (C) 1998 Elsevier Science Ltd. All rights reserved.