PEGylation of Biologies: A Multipurpose Solution

摘要

In the 1970s, life-science researchers envisioned protein therapeutics as the ultimate targeted therapy. Companies could use them to address genetic deficiencies and cancer, among other disease classes, as well as to nudge the immune system for treating autoimmune disorders. The first therapeutic proteins were derived from animal or microbial cells, so patients launched immune responses to them that could curtail their activity and produce dangerous side effects. PEGylation was initially used to prevent immune response with such drugs. PEG is polyethylene glycol, which typically exists in the form of long polymer chains. Simultaneously hydrophilic and lipophilic, water soluble, and nontoxic, PEG is synthesized from chains of ethylene oxide, which can branch or stretch to any length. Typically, PEG is linked to a protein or peptide through reactive molecular groups on amino acid side chains — most often lysine (Figure 1).