Weiliang Liu

PolyPEGylation of Protein using Semitelechelic and Mid-functional Poly(PEGMA)s synthesized by RAFT polymerization

A series of well defined semitelechelic and mid-functionalized poly(poly(ethylene glycol) methyl ether methacrylate)s (poly(PEGMA)s) were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization using thiazolidine-2-thione-functionalized chain transfer agents (CTAs). The thiazolidine-2-thione group was located either at the end or in the middle of polymer chains depending on the different structural CTAs. All polymers were fully analyzed by 1H NMR spectroscopy and GPC, confirming their well-defined structures, such as predesigned molecular weights, narrow polydispersity indices, and high yield chain-end or chain-middle functionalization. The thiazolidine-2-thione functionality located at the end of or at the middle of the polymer chains can react with amine residues on protein surfaces, forming protein-polymer conjugates via amide linkages. The bioactivity of protein conjugates were subsequently tested using micrococcus lysodeikticus cell as substitute. The protein conjugations from the mid-functionalized polymer remained much more protein bioactivity comparing to their semitelechelic counterpart with similar molecular weights, indicating the steric hindrance of the mid-functionalized poly(PEGMA)s lead to the better selective conjugation to protein. The number of polymer chains on the protein surface was additionally evaluated by TNBS analysis, exhibiting that there are less mid-functionalized poly(PEGMA)s linked on the protein surface than the semitelechelic polymers, also supporting the hypothesis that the steric hindrance from branch-structural polymers results in the better reaction selectivity. This synthetic methodology is suitable for universal proteins, seeking a balance between the protein bioactivity and the protein protection by the covalent linkage with polymer, and exhibits promising potential for pharmaceutical protein conjugation.

New optically active poly(amide-imide)s based on N,N′-(pyromellitoyl)-bis-L-amino acid and methylene diphenyl-4,4′-diisocyanate: synthesis and characterization

Five new optically active poly(amide-imide)s were synthesized through the direct polycondensation reaction between chiral N,N′-(pyromellitoyl)-bis-L-amino acids and methylene diphenyl-4,4′-diisocyanate in a medium consisting of N-methyl-2-pyrrolidone (NMP) and xylene. The resulted polymers were fully characterized by means of Fourier transform infrared spectroscopy, elemental analyses, and solubility tests. Thermal properties of these polymers were investigated by using thermal gravimetric analysis/SDTA. All of the polymers were soluble at room temperature in polar solvents such as N,N′-dimethyl acetamide, N,N′-dimethyl formamide, dimethyl sulfoxide (DMSO), NMP, sulfuric acid, and para-methyl phenol. Same specific rotations of these polymers in these different solvents were obtained.

Facile Synthesis of New Optically Active Unsaturated Amides Monomers Based on S-(+)-α-Phenyl Ethylamine

Three new optically active unsaturated amides monomers which could be polymerized were synthesized through the direct condensation between S-(+)-α-phenyl ethylamine and prop-2-enoyl chloride, 2-methyl-prop-2-enoyl chloride and undec-10-enoyl chloride, respectively. The resulted unsaturated amides were proven by means of 1H-NMR spectroscopy, FT-IR spectroscopy, elemental analyses and specific rotations. The polymerization of one of synthesized monomers, N-(1S-1-phenylethyl)-undec-10-enamide, is reported for the first time.