Enzymatic Synthesis Of The Cell Adhesive Motif Tripeptide RGD Amide In Organic Solvents

The tripeptide Arg-Gly-Asp (RGD) sequence,which was originally found within the central cell-binding domain of fibronectin,is present in a number of extracellular matrices, binds some integrins on the cell surface and contributes to cell functions including adhesion, migration and invasion. RGD-containing peptides have been reported to inhibit tumor metastasis, tumor-induced angiogenesis and tumor-elicited platelet aggregations. Therefore, the characteristic tripeptide sequence Arg-Gly-Asp (RGD) has been attracting much attention of investigators. In recent years, many researchers tried to synthesize RGD and RGD-containing peptides by chemical or enzymatic methods. As compared to the chemical method, the important benefits of enzymatic peptide synthesis are : a) the mild conditions of the reaction; b) the high regiospecifity of enzyme allowing the use of minimally protected substrates; c) the reaction being stereospecificity without racemization. Many hydrophobic small peptides were synthesized in high yield using proteases in organic media as largely reported. RGD tripeptide contains two charged amino acids (Arg and Asp) and a neutral one (Gly). Because of the low solubility of hydrophilic amino acids in organic solvents, the synthesis of hydrophilic amino acid-containing peptides generally proceeds in a rather low yield. A method available to overcome the difficulty with low solubility of hydrophilic amino acid substrates in organic solvents is to use reverse micelles as reaction media. We reported previously that the syntheses of...