Competitive profiling of ligandable cysteines in <i>Staphylococcus aureus</i> with an organogold compound

Schmidt, Claudia; Zollo, Michael; Bonsignore, Riccardo; Casini, Angela; Hacker, Stephan M.

doi:10.1039/d2cc01259f

Cited by 17 publications

(18 citation statements)

References 42 publications

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“…Auranofin treatment of mammalian cells revealed strong sensitivity of auranofin to Sec residues of Txnrd1, Gpx4, MsrB1, and Seleno under IAlabeling conditions and analyzed by MS. 179 Recently, the ligandable cysteines in Staphylococcus aureus was profiled with an organogold(III) complex using isoDTB-ABPP (isotopically labeled desthiobiotin azide-activity-based protein profiling) platform (Figure 11), which differs from the traditional ABPP by using isotopically labeled (light and heavy) desthiobiotin azide tags and is compatible with IA competition. 180 The unique C−S bond via cysteine arylation mediated by [C^N]cyclometalated Au(III) allows for an expanded or uncovered ligandable cysteines within the proteome. Overall, 108 cysteines were modified by the [C^N]-cyclometalated Au(III); interestingly, 59 cysteines were not liganded by previously screened organic electrophilic probes.…”

Section: Target Identification Of Gold Complexesmentioning

confidence: 99%

“…Indicating a broader reactivity and scope of ligand ability by Au-mediated cysteine arylation. 180 High-throughput screening with yeast deletions and gene knockdown systems including RNA interference (RNAi) and short-hairpin RNA (shRNA) to study drug−target interactions was pivotal in advancing chemical genetics. 181−186 The discovery of CRISPR-Cas9 has emerged as a powerful tool to edit the mammalian genome with ease and is useful for biological target identification, unravel mechanism of action, and resistant pathways to chemical agents.…”

Section: Target Identification Of Gold Complexesmentioning

confidence: 99%

“…Overall, 108 cysteines were modified by the [C^N]-cyclometalated Au(III); interestingly, 59 cysteines were not liganded by previously screened organic electrophilic probes. Indicating a broader reactivity and scope of ligand ability by Au-mediated cysteine arylation …”

Section: Target Identification Of Gold Complexesmentioning

confidence: 99%

Section: Target Identification Of Gold Complexesmentioning

confidence: 99%

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Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

et al. 2023

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The gold drugs, gold sodium thiomalate (Myocrisin), aurothioglucose (Solganal), and the orally administered auranofin (Ridaura), are utilized in modern medicine for the treatment of inflammatory arthritis including rheumatoid and juvenile arthritis; however, new gold agents have been slow to enter the clinic. Repurposing of auranofin in different disease indications such as cancer, parasitic, and microbial infections in the clinic has provided impetus for the development of new gold complexes for biomedical applications based on unique mechanistic insights differentiated from auranofin. Various chemical methods for the preparation of physiologically stable gold complexes and associated mechanisms have been explored in biomedicine such as therapeutics or chemical probes. In this Review, we discuss the chemistry of next generation gold drugs, which encompasses oxidation states, geometry, ligands, coordination, and organometallic compounds for infectious diseases, cancer, inflammation, and as tools for chemical biology via gold–protein interactions. We will focus on the development of gold agents in biomedicine within the past decade. The Review provides readers with an accessible overview of the utility, development, and mechanism of action of gold-based small molecules to establish context and basis for the thriving resurgence of gold in medicine.

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Section: Target Identification Of Gold Complexesmentioning

confidence: 99%

Section: Target Identification Of Gold Complexesmentioning

confidence: 99%

Section: Target Identification Of Gold Complexesmentioning

confidence: 99%

Section: Target Identification Of Gold Complexesmentioning

confidence: 99%

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Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

et al. 2023

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“…Unoxidized cysteine residues are susceptible to alkylation (Figure 7a), which is quantifiable by click chemistry‐based proteomics using IA‐alkyne (Figure 7b). [70,71] The attenuation of cysteine alkylation by IA‐alkyne can be due to treatment with a cysteine‐reactive ligand [72,73] or due to cellular redox changes. To identify redox‐sensitive cysteine residues in bacterial pathogens, quantitative proteomics with IA‐alkyne was utilized in Pseudomonas aeruginosa (PA) and SA treated with hydrogen peroxide [74] .…”

Section: Interrogating Prokaryotic Physiologymentioning

confidence: 99%

Chemoproteomic Approaches for Unraveling Prokaryotic Biology

Malarney

Chang

2023

Israel Journal of Chemistry

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Bacteria are ubiquitous lifeforms with important roles in the environment, biotechnology, and human health. Many of the functions that bacteria perform are mediated by proteins and enzymes, which catalyze metabolic transformations of small molecules and modifications of proteins. To better understand these biological processes, chemical proteomic approaches, including activity-based protein profiling, have been developed to interrogate protein function and enzymatic activity in physiologically relevant contexts. Here, chemoproteomic strategies and technological advances for studying bacterial physiology, pathogenesis, and metabolism are discussed. The development of chemoproteomic approaches for characterizing protein function and enzymatic activity within bacteria remains an active area of research, and continued innovations are expected to provide breakthroughs in understanding bacterial biology.

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Gold Complexes in Anticancer Therapy: From New Design Principles to Particle‐Based Delivery Systems

2023

Self Cite

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The discovery of the medicinal properties of gold complexes has fuelled the design and synthesis of new anticancer metallodrugs, which have received special attention due to their unique modes of action. Current research in the development of gold compounds with therapeutic properties is predominantly focused on the molecular design of drug leads with superior pharmacological activities, e.g., by introducing targeting features. Moreover, intensive research aims at improving the physicochemical properties of gold compounds, such as chemical stability and solubility in the physiological environment. In this regard, the encapsulation of gold compounds in nanocarriers or their chemical grafting onto targeted delivery vectors could lead to new nanomedicines that eventually reach clinical applications. Herein, we provide an overview of the state‐of‐the‐art progress of gold anticancer compounds, andmore importantly we thoroughly revise the development of nanoparticle‐based delivery systems for gold chemotherapeutics.

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Competitive profiling of ligandable cysteines in Staphylococcus aureus with an organogold compound

Abstract: With the idea of exploiting metal templated C–S bond forming reactions to achieve modification of cysteines in bacterial proteins, a cyclometalated Au(III) compound was explored in a competitive chemoproteomic approach...

Cited by 17 publications

References 42 publications

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

Chemoproteomic Approaches for Unraveling Prokaryotic Biology

Gold Complexes in Anticancer Therapy: From New Design Principles to Particle‐Based Delivery Systems

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