A promiscuous protein binder with redox activity efficiently promotes oxidative protein folding under condensed sub-millimolar conditions.
Efficient folding of a disulfide-containing protein, bovine pancreatic trypsin inhibitor, BPTI, can be achieved by rescuing protein kinetic traps via growth type pathways, instead of the traditional rearrangement type with glutathione disulfide, GSSG.
We report the first example of a synthetic thiol-based compound that promotes oxidative protein folding upon 1-equivalent loading to the disulfide bonds in the client protein to afford the native form in over 70% yield.
Compounds harboring high acidity and oxidizability of thiol groups permit tuning the redox equilibrium constants of CxxC sites of the PDI family enzymes and thus can be used to promote oxidative folding and increase the native protein productions by minimal loading as compared to glutathione.
New model xDLVO-CGhybr calculating second osmotic virial coefficient of protein solutions is developed. Data calculated agrees well with experiments due to accurate estimation of electrostatic protein–protein interactions using a hybrid methodology.