Abstract by Steven Draper
Chemistry and Biochemistry
How PEG can Increase Protein Conformational Stability
Polyethylene glycol (PEG) has been used to increase the serum half-life of peptide pharmaceuticals for over thirty years. We have shown previously that the effect that PEG has on a peptide varies greatly based on the position and the amino acid linker. In this work we show that PEG can stabilize a salt bridge if the original salt bridge is weak. There is a theoretical maximum stabilization that PEG can bring the salt bridge to upon PEGylation. Both the original salt bridge strength and the overall stabilization given by PEG can be predicted by measuring the dihedral angles between the salt bridge residues. If the angle is large, then the salt bridge is weak and can be stabilized by PEG. These data suggest a possible explanation for the variation in stabilization based on position and linker.