Metal assisted peptide bond hydrolysis: Chemistry, biotechnology and toxicological implications

Abstract

Metal-assisted hydrolysis of peptide bond is a promising alternative for enzymatic cleavage of proteins with prospective applications in biochemistry and bioengineering. Many metal ions and complexes have been tested for such reactivity with a number of targets, from dipeptides through oligopeptides through proteins. The majority of reaction mechanisms reported so far is based on the Lewis acidity of a given metal ion. In the alternative hydrolysis reaction the metal ion, Cu(II), Ni(II) or Pd(II), plays a structural role by forming a square planar complex with Ser/Thr–His or Ser/Thr–Xaa–His sequence, which enables a N → O rearrangement of the acyl moiety in the peptide bond downstream from the Ser/Thr residue. Both Lewis acid and N → O acyl rearrangement reaction types are discussed in detail, including molecular mechanisms, the chemical character of hydrolytic agents, reaction conditions, and the origins of differences between the results obtained for peptide and protein models. Toxicological implications and practical applications of metal assisted peptide bond hydrolysis are also presented, with a focus on the Ni(II) assisted N → O acyl rearrangement in Ser/Thr–Xaa–His sequences.