We have recently taken the surface-iniated polymerization concept to proteins. We have developed two new and general routes to grow a PEG-like polymer, poly(oligo(ethylene glycol) methyl ether methacrylate) (poly(OEGMA)), with low polydispersity and high yield solely from the N-terminus or C-terminus of a protein by in situ atom-transfer radical polymerization (ATRP) under aqueous conditions, to yield site-specific (N- or C-terminal) and stoichiometric conjugates (1:1). Protein-POEGMA conjugates show a dramatic increase in their blood exposure compared to the unmodified protein after intravenous administration to mice, thereby demonstrating that comb polymers that present short oligo(ethylene glycol) side-chains are a new class of PEG-like polymers that can significantly improve the pharmacological properties of proteins. We believe that this new approach to the synthesis of N/C-terminal protein conjugates of poly(OEGMA) may be applicable to a large subset of protein and peptide drugs, and thereby provide a general methodology for improvement of their pharmacological profiles. Current work is focused on applying this technology to pharmacologically relevant peptides and proteins.