Poly(ethylene glycol) (PEG) is a biocompatible and water-soluble polymer that has a wide range of applications in chemistry, biology, and medicine. In this dissertation, we describe the synthesis of end-functionalized PEG derivatives and PEG-like polymers for biomolecule conjugation and surface patterning applications. In Chapter 1, we provide an overview on PEG-protein conjugates, as well as current synthetic approaches and applications for protein-polymer conjugates and oligonucleotide-polymer conjugates. PEG-protein conjugates are currently the only FDA-approved protein-polymer conjugates, and the conjugation method plays an important role in protein performance. In Chapter 2, we describe a site-specific and photoinduced bioconjugation method utilizing non-covalent protein-ligand binding affinity and a photo-reactive benzophenone group. In control experiments, such as without the benzophenone group or without photo-irradiation, no PEG conjugation was observed by gel electrophoresis.
Some deficiencies of PEG such as immunological responses have been observed. Moreover, PEG does not significantly stabilize proteins in storage conditions or when stressed by heat and other factors. In Chapter 3, we describe a new type of glycopolymer with trehalose side chains, and showed its stabilizing effect toward several enzymes after heating or lyophilization. In Chapter 4, we describe the conjugation of these trehalose polymers to small interfering ribonucleic acid (siRNA) and the investigation of their properties towards nuclease resistance and serum stability.
Previously, we discovered that conjugation of comb-type PEG (oligo(ethylene glycol) (metha)crylate-based polymers) to siRNA enhanced its nuclease resistance and gene silencing efficiency. In Chapter 5, we describe the preparation of similar siRNA-polymer conjugates using the grafting from approach, meaning that polymer growth occurred from a siRNA macroinitiator. Additionally, methacrylate-based polymers with oligo(ethylene glycol) side chains have also been found to be tunable thermoresponsive polymers. In Chapter 6, we describe the use of atom transfer radical polymerization (ATRP) to synthesize three distinctly temperature-responsive oligo(ethylene glycol) methacrylate-based polymers and the preparation of thermoresponsive and fluorescent hydrogel patterns. Above their volume phase transition temperature (VPTT), the hydrogels collapsed due to the release of water, and led to fluorescent quenching. Multicomponent morphing surfaces were prepared to display dual color patterns and encrypted messages at different temperatures.
