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Synthesis overview for protein–PEG–Ad conjugates: (a) synthesis of Ad–PEG5000–Mal, a nucleophilic addition/elimination reaction; and (b) synthesis of protein–(PEG5000–Ad)x where X represents the number of PEG5000–Ad “tethers” conjugated to each molecule of protein. BSA (PDB entry 4F5S) is used as a model protein, mAb (PDB entry 1IGT) is used as a “functional example” of an antibody therapeutic. Products for mAb synthesis in (b) will also produce two fragmented antibodies (Fabs).
