Enzyme-catalyzed synthesis of site-specific and stoichiometric biomolecule-polymer conjugates

A method of making polypeptide-polymer conjugates having one or more altered pharmacological properties from a plurality of polypeptides having C-termini, the method comprising:

• a) contacting the plurality of polypeptides with a sortase and an initiator agent under conditions that permit attachment of the initiator agent to the C-terminus to form a plurality of macroinitiators;
• and
• b) incubating the plurality of macroinitiators with a monomer under conditions that permit free-radical polymerization to occur from the initiator agent to form polypeptide-polymer conjugates, such that at least about 25% of the polypeptides have a conjugated polymer initiated solely from the C-terminus,
• wherein the polypeptide-polymer conjugates have an altered pharmacological property selected from at least one of (i) an in vivo half-life that is at least 25% greater compared with the in vivo half-life of the plurality of polypeptides;
• and (ii) an in vivo biodistribution to a tissue, organ or disease site that is at least 25% greater than the in vivo biodistribution of the plurality of polypeptides.