Chemo-enzymatic synthesis of the tripeptide Bz-RGD-OEt was conducted in this study. First of all, free dipeptide, Gly-Asp was synthesized by a novel chemical method only using glycine at a large scale with low cost, followed by esterification of Gly-Asp. The linkage of the third amino acid Bz-Arg-OEt to Gly-Asp-(OEt)(2) was completed by enzymatic method in organic solvents. The effects of organic solvents, pH value, reaction temperature and water content on the yield of Bz-RGD-OEt synthesis were examined. The optimum conditions for Bz-GRD-OEt synthesis are pH 8.0, 30degreesC, in ethanol/'Fris-HCl buffer system (70:30, v/v), 5 h with the maximum yield of 72.5%. (C) 2003 Elsevier Science Inc. All rights reserved.