Synthesis of polysaccharide mimetics for bioactive surface coatings and artificial glycosylation of proteins

Natural saccharides are involved in numerous biological and although the full spectrum of their functions and mechanism has not been revealed yet, saccharides have drawn increasing interest in the biomedical field. However, the application of natural saccharides has been limited due to difficulties in their synthesis and modification.;Glycopolymers have been sought as surrogates. In this thesis, new polymerization techniques for the synthesis of saccharide mimics are discussed. Recent advancement in the synthesis of glycopolymers by controlled radical polymerization (CRP) techniques is discussed in Chapter 1.;Chapter 2 describes the synthesis of aminooxy end-functionalized poly( N-isopropylacrylamide) (pNIPAAm) by reversible addition-fragmentation chain transfer (RAFT) polymerization. pNIPAAm was conjugated to bovine serum albumin (BSA) modified with ketone groups. pNIPAAm was also immobilized on a gold surface and an aldehyde-modified heparin (a sulfated polysaccharide) was then conjugated to the pNIPAAm surface via oxime chemistry. This technique could be used for the stabilization and storage of growth factors on surfaces.;In Chapter 3, synthesis of a pyridyl-disulfide glycopolymers with N-acetyl-D-glucosamine pendant groups by atom transfer radical polymerization (ATRP) is discussed. The polymer was patterned on a surface by microcontact printing and was visualized by fluorescence microscopy. The glycopolymers was also conjugated to double-stranded short interfering RNA (siRNA). This highly efficient synthesis and one-step conjugation system offers great potential for the study of sugar-targeted siRNA gene therapy.;Chapter 4 and 5 describes the uses of sulfonated polymers as heparin mimics. In Chapter 4, poly(sodium 4-styrene sulfonate-co-poly(ethylene glycol) methacrylate) (pSS-co-pPEGMA) was synthesized via RAFT polymerization and immobilized on a gold surface. The surface was employed to study the binding of pSS-co-pPEGMA towards vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) by surface plasmon resonance (SPR). In Chapter 5, a series of sulfonated polymers were investigated as potential heparin mimics. The polymers utilized in the study were poly(sodium 4-styrene sulfonate- co-2-hydroxyethyl methacrylate) (pSS-co-pHEMA), poly(sodium poly(sodium 2-acrylamido-2-methyl propane sulfonate-co-2-hydroxyethyl methacrylate) (pAMPS-co-pHEMA), and poly(potassium 3-(methacryloyloxy)-1-propane sulfonate-co-2-hydroxyethyl methacrylate) (pSPMA-co-pHEMA). SPR studies were performed in order to screen their binding affinities to VEGF. These results suggest that these sulfonated copolymers could serve as heparin mimics.