Guanidinium‐Induced Denaturation by Breaking of Salt Bridges

Abstract

Despite its wide use as a denaturant, the mechanism by which guanidinium (Gdm + ) induces protein unfolding remains largely unclear. Herein, we show evidence that Gdm + can induce denaturation by disrupting salt bridges that stabilize the folded conformation. We study the Gdm + ‐induced denaturation of a series of peptides containing Arg/Glu and Lys/Glu salt bridges that either stabilize or destabilize the folded conformation. The peptides containing stabilizing salt bridges are found to be denatured much more efficiently by Gdm + than the peptides containing destabilizing salt bridges. Complementary 2D‐infrared measurements suggest a denaturation mechanism in which Gdm + binds to side‐chain carboxylate groups involved in salt bridges.