Synthesis And Function Of The Site-specific Polymer Hybrids

Natural produced various therapeutic peptides or proteins have more limitations due to their inherent physicochemical properties such as a variable solubility, a low bioavailability, a limited stability. A function polymer is combined with a protein by a covalent bond to form a new gaint molecule which called polymer-protein hybirds. However, the resulting hybirds can synergistically combine the properties of the polymers and overcome the separate limitations, improve protein stability, solubility and bioavailability. The hybirds can also introduce new properties such as self-assembly and phase behavior and even modulate protein activity, and they have been developed for applications in the fields of nanotechnology, catalysis, biotechnology, and drug delivery.Temperature-sensitive polymers can change their phase behavior in different temperature. The temperature-sensitive polymers-proteinshybirds can be widely used in drug delivery, bio-temperature sensitive switch, the separation of biological proteins and other fields. In this artcle we synthesized temperature-sensitive poly-N, N- diethyl acrylamide(PDEAAm) which contained some –N(CH2CH3)2groups, so the polymershave agood biocompatibility,hydrophilic and easily functional characteristics due to its amino, which widely used in environmental protection,gene therapy, drug delivery, biomedical materials and other fields.The paper studied the following three parts as follow:Chapter 1: This chapter first reviews the "smart" polymer science. First of all, we introduce a variety of "smart" polymer principles, and its synthesis and applications. Secondly, we review polymer-protein hybrids by "grafting-to ", " Grafting-from " and " Grafting-through " three grafting methods, respectively. Finally, we introduce the polemer via NMP, ATRP and RAFT four active radical formations, respectively.Chapter 2: We prepared two different initiators: linear DPS-ATRP Initiator(L-DPSBr) and two-arm DPS-ATRP Initiator(L-DPSBr) by 2,2’-pyridyl disulfide, mercaptoethanol, 2,2-bis(hydroxymethyl) propionic acid and 2-bromo isobutyryl bromide, which the functionalgroup of the pyridyl disulfide. Pyridyl disulfide is known to undergo direct coupling with free cysteines residue(Cys-34). Linear poly-N, N- diethyl acrylamide(L-PDEAAm) and two-arm poly-N, N- diethyl acrylamide(T-PDEAAm) were polymerized respectively using linear DPS-ATRP initiator(L-DPSBr) and two-arm DPS-ATRP initiator(L-DPSBr) as initiator and Cu Cl/ PMDETA as catalyst by atom transfer radical polymerization(ATRP) in distilled water and methanol mixed solution. Effect of reaction feed ratio, the temperature, reaction time and concentration of water and methanol mixed solution on the polymerization yield, the molecular weight and the degree of dispersion polymer were respectively studied in detail. 1H-NMR and GPC analyses indicate that the polymerization is well controlled with low polydispersities and big molecular weight in the optimum technological condition.Chapter 3: Polymer hybrids were synthesized with Bovine serum albumin(BSA, Cys-34) and linear poly-N, N- diethyl acrylamide(L-PDEAAm) or two-arm poly-N, N- diethyl acrylamide(T-PDEAAm) by “grafting to” technology. The product hybirds were characterized by matrix-assisted laser desorption/ ionization time of flight(MALDI-TOF), native polyacrylamidegel electrophoresis(Native-PAGE), sodium dodecyl sulfate polyacrylamidegel electropheresis(SDS-PAGE), scanning electron microscope(SEM), transmission electron microscope(TEM), ultraviolet spectrum(UV), scanning electron microscope(SEM) and transmission electron microscope(TEM) are used to test its self-assembly behavior. The results show that BSA and PDEAAm are successfully combined by covalent bond. The combination hybirds exhibits good characteristic of assembly.