Metalloproteomics for molecular target identification of protein-binding anticancer metallodrugs

Steel, Tasha R.; Hartinger, Christian G.

doi:10.1039/d0mt00196a

Cited by 29 publications

(18 citation statements)

References 108 publications

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“…After confirmation of the ability of the Re I tricarbonyl complexes to coordinate covalently bind to Cys derivatives, the binding to the SARS‐CoV‐2 3CL pro was investigated using ESI‐TOF MS [51] . While the native protein was found to have a deconvoluted mass of 33 797 (Figure S13), upon incubation with 22 for 2 h the mass shifted to 34 225 (Figure S14), corresponding to a single attached Re I tricarbonyl complex ( m / z 427).…”

Section: Resultsmentioning

confidence: 99%

Re^I Tricarbonyl Complexes as Coordinate Covalent Inhibitors for the SARS‐CoV‐2 Main Cysteine Protease

et al. 2021

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Since its outbreak, the severe acute respiratory syndrome—coronavirus 2 (SARS‐CoV‐2) has impacted the quality of life and cost hundreds‐of‐thousands of lives worldwide. Based on its global spread and mortality, there is an urgent need for novel treatments which can combat this disease. To date, the 3‐chymotrypsin‐like protease (3CLpro), which is also known as the main protease, is considered among the most important pharmacological targets. The vast majority of investigated 3CLpro inhibitors are organic, non‐covalent binders. Herein, the use of inorganic, coordinate covalent binders is proposed that can attenuate the activity of the protease. ReI tricarbonyl complexes were identified that demonstrate coordinate covalent enzymatic inhibition of 3CLpro. Preliminary studies indicate the selective inhibition of 3CLpro over several human proteases. This study presents the first example of metal complexes as inhibitors for the 3CLpro cysteine protease.

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Section: Resultsmentioning

confidence: 99%

Re^I Tricarbonyl Complexes as Coordinate Covalent Inhibitors for the SARS‐CoV‐2 Main Cysteine Protease

et al. 2021

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“…We envision that an integrated omics approach to determine the changes in the proteome, metabolome and metalloproteome will offer a comprehensive view of the pathogen response to nutritional immunity as well as Fe overload. Recently, integrated omics approaches have been successfully used to explore the molecular action of metallodrugs such as platinum and ruthenium anticancer drugs ( Wang, Li, and Sun 2019 ; Steel and Hartinger 2020 ). Of key importance will be metalloproteomics, which will provide information on the changing intracellular metal distribution among S. aureus ’ proteins.…”

Section: Discussionmentioning

confidence: 99%

The Role of Iron in Staphylococcus aureus Infection and Human Disease: A Metal Tug of War at the Host—Microbe Interface

Dijk

Kruijff

Hagedoorn

2022

Front. Cell Dev. Biol.

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Iron deficiency anemia can be treated with oral or intravenous Fe supplementation. Such supplementation has considerable effects on the human microbiome, and on opportunistic pathogenic micro-organisms. Molecular understanding of the control and regulation of Fe availability at the host-microbe interface is crucial to interpreting the side effects of Fe supplementation. Here, we provide a concise overview of the regulation of Fe by the opportunistic pathogen Staphylococcus aureus. Ferric uptake regulator (Fur) plays a central role in controlling Fe uptake, utilization and storage in order to maintain a required value. The micro-organism has a strong preference for heme iron as an Fe source, which is enabled by the Iron-regulated surface determinant (Isd) system. The strategies it employs to overcome Fe restriction imposed by the host include: hijacking host proteins, replacing metal cofactors, and replacing functions by non-metal dependent enzymes. We propose that integrated omics approaches, which include metalloproteomics, are necessary to provide a comprehensive understanding of the metal tug of war at the host-microbe interface down to the molecular level.

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“…The studies about interactions of metallodrugs with intracellular proteins attract significant attention since they have relevant pharmacological consequences. [27][28][29][30][31][32][33][34][35][36][37][38][39] Cytochrome c is a vital mitochondrial protein that plays important roles in oxi-dative phosphorylation and apoptosis. [40][41][42] Cytochrome c is reported to facilitate the reduction of satraplatin and t,c,c-bis (acetato)diaminedichloroplatinum(IV) in the presence of the electron donor nicotinamide adenine dinucleotide (NADH).…”

Section: Introductionmentioning

confidence: 99%

Interactions between mitochondria-damaging platinum(iv) prodrugs and cytochrome c

Zheng

Jayawardhana

2022

Dalton Trans.

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Metalloproteomics for molecular target identification of protein-binding anticancer metallodrugs

Abstract: The development of the metallodrug pull-down as a metalloproteomic technique has enabled the identification of the protein targets of metal-based anticancer agents.

Cited by 29 publications

References 108 publications

Re^I Tricarbonyl Complexes as Coordinate Covalent Inhibitors for the SARS‐CoV‐2 Main Cysteine Protease

Re^I Tricarbonyl Complexes as Coordinate Covalent Inhibitors for the SARS‐CoV‐2 Main Cysteine Protease

The Role of Iron in Staphylococcus aureus Infection and Human Disease: A Metal Tug of War at the Host—Microbe Interface

Interactions between mitochondria-damaging platinum(iv) prodrugs and cytochrome c

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Metalloproteomics for molecular target identification of protein-binding anticancer metallodrugs

Abstract: The development of the metallodrug pull-down as a metalloproteomic technique has enabled the identification of the protein targets of metal-based anticancer agents.

Cited by 29 publications

References 108 publications

ReI Tricarbonyl Complexes as Coordinate Covalent Inhibitors for the SARS‐CoV‐2 Main Cysteine Protease

ReI Tricarbonyl Complexes as Coordinate Covalent Inhibitors for the SARS‐CoV‐2 Main Cysteine Protease

The Role of Iron in Staphylococcus aureus Infection and Human Disease: A Metal Tug of War at the Host—Microbe Interface

Interactions between mitochondria-damaging platinum(iv) prodrugs and cytochrome c

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Product

Resources

About

Re^I Tricarbonyl Complexes as Coordinate Covalent Inhibitors for the SARS‐CoV‐2 Main Cysteine Protease

Re^I Tricarbonyl Complexes as Coordinate Covalent Inhibitors for the SARS‐CoV‐2 Main Cysteine Protease