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

RGD tripeptide as the cellular adhesion factor was synthesized by a combination of chemical and enzymatic methods in this study. First of all, Gly-Asp diamide was synthesized by a novel chemical method in three steps including preparation of L-aspartic acid dimethyl ester, chloroacetylation of L-aspartic acid dimethyl ester and ammonolysis of chloroacetyl L-aspartic acid dimethyl ester. Secondly, Porcine Pancreas Lipase (PPL) was used to catalyze the synthesis of Benzyl-Arg-Gly-Asp diamide in water-organic cosolvents systems. The reaction condition was optimized by examining the main factors affecting the yield of the tripeptide. The optimal reaction condition was set up as pH7.7, 15°C 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 tripeptide yield of 71.7%.