Unexpected impact of the number of glutamine residues on metal complex stability

Abstract

The emerging question which this study aims to answer is: what impact do glutamines have on the stability of metal–peptide complexes? We focused our attention on the N-terminal domain of Hpn and Hpn-like proteins from Helicobacter pylori. Cu²⁺ and Ni²⁺ complexes of the model peptides MAHHE-NH₂, MAHHEEQ-NH₂, MAHHEQQ-NH₂ and MAHHEQQHQA-NH₂ were studied by means of different thermodynamic and spectroscopic techniques, as well as through molecular modelling computation. Experimental results, in very good agreement with theoretical findings, lead to the not obvious conclusion that the stability of metal complexes distinctly increases with the number of glutamine residues present in the peptide, although glutamine side-chains do not directly take part in coordination. This peculiar finding allows one to look at polyglutamine sequences, not only the ones present in some bacterial chaperones but also those involved in several neurodegenerative diseases, from a new perspective.