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Determination of Relative Stabilities of Metal‐Peptide Bonds in the Gas Phase
Author(s) -
Cziferszky Monika,
Truong Dianna,
Hartinger Christian G.,
Gust Ronald
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202102385
Subject(s) - gas phase , peptide , phase (matter) , metal , chemistry , materials science , organic chemistry , biochemistry
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.