Abstract by Natalie Becar

Personal Infomation

Presenter's Name

Natalie Becar



Degree Level



Steven Draper
Paul Lawrence
Wendy Billings
Qiang Xiao
Nathaniel Brown
Derek Matheson

Abstract Infomation


Chemistry and Biochemistry

Faculty Advisor

Josh Price


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


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.