Control of rHuEPO biological activity: the role of carbohydrate.

Objective: Darbepoetin alfa, a novel erythropoiesis-stimulating protein, is a glycosylation analog of recombinant human erythropoietin (rHuEPO) with two additional N-linked carbohydrates. Used to treat anemia of cancer, chemotherapy, and kidney disease, it has a three-fold longer serum half-life and increased in vivo activity, but decreased receptor-binding activity. Glycosylation analogs with altered N-linked carbohydrate content were compared with rHuEPO to elucidate the relationship between carbohydrate content and activity.