The Invesigation Of Zwitterionic Block Copolymers In Protein Coniugation

With the development of science and technology in genomics, biochemistry, molecular biology and peptide synthesis, protein drugs are becoming very important ones and have been widely used in clinical. Compared to traditional small molecule drugs, protein drugs show high activity, high specificity, low toxicity, and clearly biological functions to clinical characteristics. However, the low stability, fast clearance and immunogenicity of protein drugs become the major hindrances in their efficient clinical applications. Thus, the modification of protein drugs becomes a more and more vital method to improve the efficiency of protein drug in clinic.In this work, two types of zwitterionic block copolymer PMAA-b-CBMA and PMAA-b-SBMA were synthesized via atom transfer radical polymerization (ATRP) for protein modification. Results show that the modification of the model protein, bovine serum albumin (BSA), by PMAA-b-SBMA (abbreviated as PMS) was more efficient than by PMAA-b-CBMA (abbreviated as PMC). And the best conjugated result is obtained under the condition of10times PMS,150times1-Ethyl-3-(3-dimethyllaminoproyl) carbodiimide hydrochloride (EDC) and1-Hydroxy-2,5-pyrrolidinedione (NHS) of BSA (molar ratio), and the pH5.3of reaction buffer. The conjugates could be separated through precipating at pH5.3, and redissolving in PBS, pH7.5.The conjugates of PMS-2-uricase show a higher biological activity and smaller Michaelis constant Km than those of native uricase. Furthermore, the conjugates exhibit higher stability to trypsin digestion than native protein while the stabilities of the conjugates to the temperature, pH and the ionic strength were similar to those of native protein.Therefore, it suggests that the modification of protein drugs by the noufouling zwitterionic polymer could be widely applied for future clinical application.