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Abstract by Natalie Becar

Personal Infomation


Presenter's Name

Natalie Becar

Degree Level

Undergraduate

Abstract Infomation


Department

Chemistry and Biochemistry

Faculty Advisor

Josh Price

Title

PEG-based increases to conformational and proteolytic stability of a Beta-sheet protein depends on PEGylation strategy and location

Abstract

Polyethylene Glycol (PEG) has many beneficial pharmacokinetic properties and when strategically incorporated onto a protein drug significantly enhances conformational stability and proteolytic resistance. Some protein drugs can have short-circulating half-lives, are degraded by proteolytic enzymes, and are often neutralized by anti-bodies. However, aside from avoiding enzyme active sites or protein-binding interfaces, there are few guiding principles that can consistently predict optimal PEGylation sites. We demonstrate that the identity of the PEG-protein linker plays a substantial role on conformational stability of Beta-sheet model protein WW. The results of testing several Protein-PEG linkers show that some linkers are more effective at specific sites than others; for example, PEGylation of propargyloxyphenylalanine is stabilizing at the same site where Asn-PEGylation is destabilizing. Interestingly, the conformational stability observed correlated to proteolytic resistance.