Determination of Relative Stabilities of Metal-Peptide Bonds in the Gas Phase

Understanding binding site preferences in biological systems as well as affinities to binding partners is a crucial aspect in metallodrug development. We here present a mass spectrometry-based method to compare relative stabilities of metal-peptide adducts in the gas phase. Angiotensin 1 and substance P were used as model peptides. Incubation with isostructural N-heterocyclic carbene (NHC) complexes of Ru-II, Os-II, Rh-III, and Ir-III led to the formation of various adducts, which were subsequently studied by energy-resolved fragmentation experiments. The gas-phase stability of the metal-peptide bonds depended on the metal and the binding partner. Of the four complexes used, the Os-II derivative bound strongest to Met, while Ru-II formed the most stable coordination bond with His. Rh-III was identified as the weakest peptide binder and Ir-III formed peptide adducts with intermediate stability. Probing these intrinsic gas-phase properties can help in the interpretation of biological activities and the design of site-specific protein binding metal complexes.

Automated summary

This study proposed a mass spectrometry-based method to compare the relative stabilities of metal-peptide adducts in the gas phase, revealing that the gas-phase stability of the metal-peptide bonds depends on the metal and the binding partner. Detection of these intrinsic gas-phase properties can aid in understanding biological activities and designing site-specific protein binding metal complexes.