Studies On The Synthesis Of Tetrapeptide GRGD And Pentapeptide GRGDS

The bioactive RGD related peptides are the basic conformation in all kinds of matrix protein and the basic recognized site between cells. RGD, as the recognized site between the integrin and the extracellar matrix, send the ligand and the acceptor to combine so as to bring a series of biochemical changes. The important function of RGD is to advance the cell adhesion, this adhesion has become the new target in drug design, especially in the biomaterials. hi present, RGD is used as the compatibility of the biomaterials, anti-thrombus, anti-tumor, vasodilation and the endothelial cells growth on the material surface. RGD containing peptides and derivatives are the potential peptide-drugs.hi the present paper, two peptides, tetrapeptide Gly-Arg-Gly-Asp and pentapeptide Gly-Arg-Gly-Asp-Ser, were synthesized through liquid-phrase synthesis.This synthesis started with the protection of the amino acid, successfully protecting the amino, the carbonyl and the guanidine of argine , gaming these intermediates: BocGly, BocArg(N02)OH, SerOBzl, BocAsp(Obzl)OH, Asp(OBzl). These intermediates were confirmed by TLC, infrared spectra and melting point. In synthesizing the Boc-Gly, researched that temperature influences the reaction. The experiment indicated that temperature is the important factor that influences the reaction. Researched the synthesis of SerOBzl in three aspects: temperature, ratio of the material and the catalyst, tune. Found out the optimal route: selecting the benzene as the co-boiling thing; refluxing at 105℃-110℃ of the oil-bath temperature; the ratio of the material and the catalyst is 1:1.2.Selected the reverse synthetical route beginning from the last ammo acid. HOBt, DCC used as the coupling agents, NMM used to regulate pH, THF and DMF used as solvent, TFA used as deprotecting reagent, in the last all protecting groups were removed from the protected peptide by catalytic hydrogenolysis over palladium-carbon. The crudes were purified by silica gel thin layer plates and the crude peptides were purified by recrystallization using EtOH and H₂O. TLC, Products were confirmed by infrared spectra, mass spectrometry, melting point, TLC. The sequence of amino acid was confirmed by the amino acid analysis. The experimental data indicated that in the liquid-phrase synthesis using HOBt, DCC and NMM as coupling agents and TFA for deprotection of Boc might be a good way of combination for synthesis.