N-TERMINAL MODIFIED PEG-TRAIL, METHOD FOR PREPARING AND USES THEREOF

摘要

A N-terminal modified PEG(polyethylene glycol)-TRAIL(tumor necrosis factor related apoptosis inducing ligand) is provided to reduce liver toxicity, increase the in vivo retention time, and enhance solubility and stability in solution and pharmacokinetic profiles of TRAIL, so that it is useful for prevention and treatment of proliferative disease and autoimmune disease. A N-terminal modified PEG-TRAIL having non-toxicity to the liver is prepared by linking PEG or PEG derivatives specifically to the N-terminal of TRAIL, wherein PEG is selected from methoxy polyethylene glycol succinimidyl propionate, methoxy polyethylene glycol N-hydroxysuccinimide, methoxy polyethylene glycol aldehyde, methoxy polyethylene glycol maleimide and multi-branched type polyethylene glycol, and the TRAIL contains a zipper amino acid array inducing trimer formation or a terminal group for facilitating the separation and purification.