Synthesis and application of DNA containing hybrid block copolymers

Abstract

DNA containing hybrid materials have been extensively used in the areas of biosensor, imaging, drug delivery, and morphological studies due to their unique ability of hybridization. Typically, DNA segment provides biological functions and the connected synthetic material preserves its characteristics. In this thesis, various types of DNA conjugates and DNA block copolymers are synthesized, and applied to study more complex systems. In Chapter 4, influence of DNA-lipid conjugates in phospholipid recruitment behavior is examined. 15-nm of DNA marked AuNPs are prepared and hybridized with cDNA or cDNA-lipid conjugate to provide different surface functionalities. Then liposomes are added to induce supported lipid layer formation. It is found when liposomes are in large excess, surface chemistry dictates that lipid bilayer forms on cDNA containing target surface while lipid monolayer forms on cDNA-lipid surfaces. When there are less available liposomes, surface chemistry is overcome and lipids are more actively recruited on cDNA-lipid containing surfaces. Among different lipid compositions, POPS system shows best selectivity towards lipid recruitment between cDNA and cDNA-lipid surfaces attributed to reduced charge interaction with anionic DNA segments and modulated lipid penetration. In Chapter 5, various types of DNA diblock copolymers are synthesized through a chemical route. Then the diblock copolymers are connected by ligation enzyme to generate covalently linked DNA triblock copolymers. These triblock copolymers show higher stability than hybridization driven DNA triblock copolymers. In Chapter 6, the triblock formed through a ligation reaction was further digested by restriction enzyme, allowing for DNA diblock regeneration. Next, beyond a single restriction site incorporation, a multiple cloning site is inserted in the DNA triblock copolymer. Using the same strategy, diblocks of different DNA lengths are regenerated from a common parent DNA triblock. They are then connected to a new set of diblocks to create a range of versatile ABA and ABC type DNA triblock copolymers. Through the reported method, a simple transition from a single triblock to a different triblock(s) was realized.