Lipase-catalyzed synthesis of RGD diamide in aqueous water-miscible organic solvents

RGD tripeptide as the cellular adhesion factor was synthesized by a combina tion of chemical and enzymatic methods in this study. First of all, Gly-Asp diamide was synthesized by a novel chemical method in three steps includin g preparation of L-aspartic acid dimethyl ester, chloroacetylation of L-asp artic acid dimethyl ester and ammonolysis of chloroacetyl L-aspartic acid d imethyl ester. Secondly, Porcine Pancreas Lipase (PPL) was used to catalyze the synthesis of Benzyl-Arg-Gly-Asp diamide in water-organic cosolvents sy stems. The reaction condition was optimized by examining the main factors a ffecting the yield of the tripeptide. The optimal reaction condition was se t up as pH7.7, 15 degreesC in 50% DMF for 8 h with the maximum yield of 76. 4%. It was also found that 50% DMSO was another alternative with the tripep tide yield of 71.7%. (C) 2001 Elsevier Science Inc. All rights reserved.