N- TERMINAL PEG CONJUGATE OF ERYTHROPOIETIN

摘要

The present invention refers to conjugate of erythropoietin having higher bioactivity comprises an Erythropoietin glycoprotein having N-terminal a - amino group and aldehyde derivatives of polyethylene glycol, said erythropoietin glycoprotein being selected from the group consisting of human erythropoietin and analogs thereof, said aldehyde derivative of methoxy polyethylene glycol of the formula: PEG-R-CHO wherein R= alkyl group of formula -(CH₂)_n wherein n=2 to 4. The formula of the conjugate of the present invention is: PEG-R-CONH-EPO wherein R=alkyl group of formula -(CH₂)_n wherein n=2 to 4. Said erythropoietin according to the present invention is a recombinant erythropoietin (rhEPO) produced in animal cells; said erythropoietin conjugate is prepared by expressing, fermenting, and purifying rhEPO protein in recombinant animal cells and reacting EPO with PEG- Aldehyde to obtain N-terminally pegylated EPO by reductive amination reaction and then further purified to obtain pure N-terminally pegylated EPO.