Scheme 13. Acid-catalyzed hydrolysis and alcoholysis. (A) A general reaction scheme of acid-catalyzed hydrolysis/alcoholysis. (B) Structures of representative metal catalysts that mediate protein-backbone cleavage. (C) Chemical strategies that enhance the catalytic hydrolysis and alcoholysis. Top: Backbone hydrolysis accelerated by the copper center as Lewis acid and reversible formation of imine inducing proximity-driven effects. Bottom left: Nterminal specific cleavage by a CoIII catalyst. Bottom right: Catalytic acylation of alkylalcohols on proteins accelerated by an acid-activated carboxylic acid used as a solvent.