UC Irvine

The interactions between synthetic affinity agents and biomacromolecules are reported to be due to the various intermolecular interactions that occur between them during binding. Among them, hydrophobic interactions play a large role. Changes in hydrophobicity, either due to changes in incorporation or in hydrophobicity of the monomers used, can often change more than just biomacromolecular affinity. By changing the chemical composition, the physical properties and structure of the abiotic affinity agents can also be affected. It is therefore important to study how changes in hydrophobicity can affect the polymer affinity reagents and their biomacromolecular targets. This information can then be used to enhance and optimize binding to biomacromolecules. In Chapter 1, I discuss the effect of hydrophobicity on the structure and affinity of synthetic affinity agents, and how the structure and function of the biomacromolecules that interact with them are affected.

In Chapter 2, we describe how NiPAm based copolymer nanoparticles (NPs) containing C4 – C8 hydrophobic groups were used to optimize affinity to molecules with lipid-like domains. Using NMR spectroscopy, we found that optimizing interactions between NPs and lipopolysaccharides require maximizing hydrophobicity while avoiding side chain aggregation.

In Chapter 3, we describe how these NPs can be engineered as autonomous polymer heat shock proteins that prevent denaturation of biomacromolecules. By studying the effect of different hydrophobic monomers, we found that hydrophobic interactions can affect not only affinity, but activity of the synthetic affinity agents against biomacromolecules.

In Chapter 4, we discuss a novel end-cap for self immolative polymers that is active against cysteine. We tested this novel end-cap as a protective group on a monomer and oligomer, in solution and as a film, and found that it was selective for cysteine, and could remain stable in atmospheric conditions.