Synthesis, Pegylation And Analysis Of Anti-adhension LDV And LDV Derivative With Anti-inflammatory, Immune Activities

Object: Very late antigen-4(VLA-4)plays an important role in inflammatory processes by regulating the migration and exudation of leukocytes into inflamed tissues. Now, it is widely regarded as a new target for anti-inflammation drug. VLA-4 mediates cell adhesion by binding to either of two protein ligands, vascular cell adhesion molecule-1(VCAM-1)or the alternatively spliced connecting segment 1-containing fibronecitn(FN)variant. LDV(Leu-Asp-Val)is the key sequence that attached to FN ligand. In recent years, the study on small molecule peptide VLA-4 antagonist based on tripeptide LDV has become a hot topic. However, like other small molecule peptide drugs, they are lack of enzyme stability, rapid elimination and short plasma half-life.PEG (Polyethylene glycol)is a nontoxic, nonimmuno -genic, biocompatible, and water-soluble polymer used in biotechnology , biomaterials, and pharmaceutics. PEG derivatives, covalently attached polyethylene glycol toproteins and peptides (PEGylation), have been used to enhance drug stability, plasma half-life, while reducing toxicity, proteolysis, and clearance. Since 1990, several PEGylated proteins have...