The tripeptide Arginyl-Glycyl-Aspartic acid (RGD) is a common cellrecognition site of many adhesive proteins contained in extracellularmatrices and in the blood . It binds some integrins on the cell surface andconstitute a versatile recognition system providing cells with anchorage,traction for migration and signals for polarity, position, differentiation andgrowth. Recently, research on RGD and its derivatives has become a hotspot, mainly because RGD-containing peptides and proteins havetherapeutic value in pathology, they can bind competitively to target sites,block the adhesive proteins-induced generation of some diseases, and canalleviate some diseases as well. For instance, they have been found to beuseful in anti-metastasis, anti-thrombosis, and treating osteoporosis, theyalso have therapeutic value in acute renal failure and in the recovery fromburn after operation.In recent years, many researchers tried to synthesize RGD andRGD-containing peptides by chemical or enzymatic methods. As comparedto the chemical method, the important benefits of enzymatic peptidesynthesis are : a) the mild conditions of the reaction;b) the highregiospecifity of enzyme allowing the use of minimally protected substrates;c) the reaction being stereospecificity without racemization. Manyhydrophobic small peptides were synthesized in high yield using proteasesin organic media as largely reported. RGD tripeptide contains two chargedamino acids (Arg and Asp) and a neutral one (Gly). Because of the lowsolubility of hydrophilic amino acids in organic solvents, the synthesis ofhydrophilic amino acid-containing peptides generally proceeds in a ratherlow yield. A method available to overcome the difficulty with low solubilityof hydrophilic amino acid substrates in organic solvents is to use reversemicelles as reaction media. We reported previously that the syntheses ofprecursor dipeptides of RGD catalyzed by proteases under thermodynamiccontrol and kinetic control in reverse micelles were conducted withreasonable yields. But it should be pointed out that the presence ofsurfactant molecules in the reaction system makes separation andpurification of peptide products difficult.In this study, aqueous medium is used to prepare the water-solubilityprecursor tripeptide. Although large amount of water will make the productsynthesized hydrolyzed, we have got the precursor tripeptideBz-RGD-OMe by selecting a kind of cysteine proteinases -papain tocatalyze the synthesis reaction, with kinetical control and proper reactionsystem, and we get a reasonable transfer yield. The effects of differentfactors, including water content, temperature, reaction time and molar ratioof the substrates, on the Bz-RGD-OMe synthesis were examined andoptimized. Furthermore, free RGD tripeptide has been synthesized by liquidphase synthesis methodThe other part of my work is initially research on how toencapsulate RGD into PLA(polylactic acid) microsphere. Because RGDitself can be clear off very quickly in vivo. Only if they combine with othermaterials, can they stay longer. To prepare RGD-PLA microsphere, weadopt a method solvent evaporation in which PLA-CH2Cl2 solution andglutin aqueous solution are as disperse phase and continuous phaserespectively, and established the optimal preparation condition byorthogonal design method. We examined the product in respects of itsmodality、size and encapsulization yield. As a result, we get the RGD-PLAmicrosphere with fine shape and proper size, and the highestencapsulization yield is 83.124%。On the whole, I mainly discuss the synthesis of water-solubletripeptide precursor in full aqueous medium, and research the optimalreaction conditions. Moreover, I also synthesize some RGD tripeptide byliquid phase synthesis method, and study initially about the prepatation ofits PLA microsphere at last. All these work can be the basis of its laterapplication in physiological experiment and further development asmedicine.