N-Gemini peptides: cytosolic protease resistance via N-terminal dimerization of unstructured peptides
Fayer, E.L.; Gilliland Jr, W.M.; Ramsey, J.M.; Allbritton, N.L.; Waters, M.L. N-Gemini peptides: cytosolic protease resistance via N-terminal dimerization of unstructured peptides. Chem. Commun. 2018, 54, 204-207.
Herein we describe a synthetically simple strategy for increasing the lifetime of unstructured peptides in cytosolic environment via dimerization at the N-terminus to block threading into the catalytic cleft of cytosolic proteases. We establish this approach with kinase substrates, allowing for phosphorylation in cells as a demonstration of protease resistance.