Proteins have proven to have tremendous potential in biological pharmaceuticals and drug targets due to their highly specific and complex set of functions and biocompatibility. In many cases, the key to successfully utilizing proteins for these applications is maintaining conformational stability and desired function. There is widespread interest in the use of water-soluble polymers such as neutral poly(ethylene glycol) (PEG) and zwitterionic poly(sulfobetaine) (pSB) to stabilize proteins in solution due to their assumed low binding to proteins. However, differences in PEG and pSB-protein interaction mechanisms have yet to be completely understood. For example: despite the existence of complementary charged and polar patches on pSB and proteins, why would pSB not interact with proteins? Here it is demonstrated that poly(zwitterion) chains in solution can actually interact with proteins directly, reduce the thermal stability, and increase the protein folding cooperativity relative to proteins in buffer solutions. pSB was synthesized using atom transfer radical polymerization and characterized using end group analysis and dynamic light scattering. Polymer-protein interactions were investigated using tryptophan fluorescence emission spectra and thermal denaturation studies on three structurally-distinct proteins. This research reveals that pSB is not universally protein-repellent and its efficacy in biotechnology will depend on the specific protein used.

Soluble zwitterionic poly(sulfobetaine) destabilizes proteins

2019 Spring National Meeting

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