Semi-enzymatic acceleration of oxidative protein folding by -methylated heteroaromatic thiols.

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. -Methylation is a central post-translational processing of proteins for regulating functions including chaperone activities. Despite the universally observed biochemical reactions in nature, -methylation has hardly been utilized in the design, functionalization, and switching of synthetic bioregulatory agents, particularly folding promotors.

Cysteine-based protein folding modulators for trapping intermediates and misfolded forms.

Folding is a key process to form functional conformations of proteins. Folding on-pathway intermediates leads to the formation of native structures, while folding through off-pathways affords non-native and disease-causing forms. Trapping folding intermediates and misfolded forms is important for investigating folding mechanisms and disease-related biological properties of the misfolded proteins.