Competitive LC-MS/MS assay to investigate protein metalation dynamics.

ABSTRACT: Knowledge gaps in the biospeciation of potential metallodrugs may lead to the generalized assumption of their promiscuous reactivity and inherent toxicity, neglecting their pharmaceutical potential. Herein, we developed a rapid and competitive LC-MS/MS assay to determine metalation dynamics of protein mixtures by metallodrugs. Specifically, the time-dependent reactivity of different metallodrugs, based on platinum(ii) (cisplatin, [Pt(ala)(ASA-But)Cl]), ruthenium(ii) ([Ru(HQ)(Cym)Cl], [Ru(NHC)(Cym)Cl₂]), and iridium(iii) ([Ir(HQ)(Cp*)Cl], [Ir(NHC)(Cp*)Cl₂]), towards an equimolar protein mixture was investigated. The assay revealed metal-dependent selectivity of adduct formation and subsequent deactivation by cellular detoxifying nucleophiles, e.g. glutathione (G

SUBMITTER: Kussner K 

PROVIDER: S-EPMC12935058 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature