Patent ID: 7927579

Claim:
A method for modification of a target group in or near a secondary ligand binding site of a protein comprising: contacting the protein with at least one site-specific activated polymer complex comprising: a functional group reactive with the target group; a polymer linked to the functional group; and a ligand moiety that specifically binds to the secondary ligand binding site, thereby effecting site-specific covalent bonding of the target group on the protein via the functional group, and eliminating the ligand moiety from the protein-polymer conjugate after the specific covalent bonding of the target group on the protein, wherein the functional group is selected from the group consisting of: a dithioester; a thioloester; thionoester; a selenoester; a selenoloester; a selenonooester; a phosphonoester; a phosphoric ester; a phosphinic ester; a sulfonate ester; a diazoester; an acylphosphate; an o-salicylate; a p-salicylate; a m-salicylate; a disulfide; and an α-keto- or β-keto acid or ester; wherein the polymer is a polyethylene glycol polymer; wherein the secondary site-specific ligand moiety is a peptidyl ligand moiety or carbohydrate ligand moiety; and wherein the secondary ligand binding site is a site differing from a primary binding site; and wherein the secondary ligand binding site has no effect on the primary function of the protein.