Abstract by Zachary Jones
Chemistry and Biochemistry
Extending Proteolytic Stability Using Inter-helical PEG Stapling Techniques
Protein therapeutics’ popularity is growing; however, major challenges still exist that prevent the broader application of treatments. Short serum half-life, caused by renal clearance and enzymatic proteolysis, can be addressed and improved through PEGylation. Price lab has shown that a PEG staple can further enhance the proteolytic and conformational stability of a peptide and small protein, after applying stapling broadly to β-sheet dominated peptides and the small protein SH3. To generalize broader application of PEG stapling, we have applied a PEG staple to the GCN-4 heterodimer system, further stabilizing the helical system by -.9 kcal/mol. We look forward to applying this technique to larger α-helical bundled proteins with pharmaceutical applications.