Chemo-enzymatic Syntheses Of Cellular Adhesion Motif RGD (S) And Effects Of Their Anti-tumor Cellular Adhesion

Many proteins present in extracellar matrix(ECM)and blood plasma,contain a common tripeptide amino acid sequence Arg-Gly-Asp(RGD)as a recognition site for cellular adhesion,spreading and motility of cells. The RGD motif plays a key role in mediating integrin-matrix interaction and signals transmission , which modulate cell-survival and function. RGD-containing peptides as competitive,reversible inhibitors for the binding of adhesive proteins have been widely used to study adhesive interaction between cells and inhibit tumor metastasis,tumor induced angiogenesis and tumor elicited platelet aggregations. RGD peptides not only play a major role as anchoring molecules but also are important in processes like embryogenesis,cell differentiation,immune-response. X₁-RGD-X₂(X₁ =Gly,Asp;X₂ =Ser,Cys,Val,Phe),which is the further extension of the RGD, have been reported to make these sequences be even more efficient adhesion motifs to integrins of cell membrane. For example,RGDS peptide exhibits additional potent anti-chemotactic and pro-apoptotic effects independently from its anti-adhesive action,likely by entering the cells and directly activating caspase 8 and 9,and lately caspase 3,implying unexpected intracellular actions of the RGD-motif. In addition,it was also reported that the activity of RGDS is improved upon acetylation of the N-terminus at arginine and amidation of serine at the C-terminus(Ac-RGDS-NH₂).As we know,it is not available to isolate RGD or other biologically active peptides from whole tissue directly. So many researchers tried to...