Synthesis of uniform protein-polymer conjugates.
We have developed a novel technique to synthesize near-uniform protein-polymer conjugates by initiating atom transfer radical polymerization of monomethoxy poly(ethylene glycol)-methacrylate from 2-bromoisobutyramide derivatives of chymotrypsin (a protein-initiator). Polymerization initiated from the monosubstituted protein-initiator resulted in the conjugate containing a single, near-monodisperse polymer chain per protein molecule with polydispersity index 1.05. Increasing the number of conjugated 2-bromoisobutyramide initiators per molecule of protein increased the molecular weights and polydispersity indices of the final protein-polymer conjugates. The generic nature of this technique was demonstrated by initiating polymerization of nonionic, cationic, and anionic monomers from the protein-initiator. Protein-polymer conjugates synthesized by this novel technique retained 50-86% of the original enzyme activity. The technique described herein should be useful in synthesizing well-defined protein-polymer conjugates exhibiting a wide range of physical and chemical properties.
Lele
Bhalchandra S
BS
Department of Bioengineering, Room 513, University of Pittsburgh, Pittsburgh Pennsylvania 15219, USA.
Murata
Hironobu
H
Matyjaszewski
Krzysztof
K
Russell
Alan J
AJ
D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions; D001672:Biocompatible Materials / Q000737:chemistry*; D002384:Catalysis; D002417:Cattle; D002918:Chymotrypsin / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry; D008956:Models, Chemical; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010179:Pancreas / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry*; D019163:Reducing Agents / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D014357:Trypsin / Q000737:chemistry / Q000494:pharmacology
D000577:Amides; D000838:Anions; D001672:Biocompatible Materials; D046911:Macromolecular Substances; D008689:Methacrylates; D010455:Peptides; D011108:Polymers; D011506:Proteins; D019163:Reducing Agents; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C006866:butyramide; D002918:Chymotrypsin; D014357:Trypsin; C049840:2-(dimethylamino)ethyl methacrylate