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Veronika Šlachtová

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

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Milan Vrábel

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Lucie Brulíková

Palacký University Olomouc

Simona Bellová

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Martin Dračínský

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Rastislav Dzijak

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Helena Mertlíková‐Kaiserová

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Juraj Galeta

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Davie Cappoen

Sciensano (Belgium)

Peter Rukovanský

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Michal Rahm

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Cooperative Institutions

Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Czech Academy of Sciences

Palacký University Olomouc

University of Antwerp

Charles University

TU Wien

Provincial Institute for Hygiene

Ghent University

Institute of Molecular and Translational Medicine

Bioscience Research

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Sulfonated Hydroxyaryl‐Tetrazines with Increased pKa for Accelerated Bioorthogonal Click‐to‐Release Reactions in Cells

Angewandte Chemie International Edition (2024)

Michal Rahm Patrick Keppel Rastislav Dzijak Martin Dračínský Veronika Šlachtová

Bioorthogonal reactions that enable switching molecular functions by breaking chemical bonds have gained prominence, with the tetrazine‐mediated cleavage of trans‐cyclooctene caged compounds (click‐to‐release) being particularly noteworthy for its high versatility, biocompatibility, and fast reaction rates. Despite several recent advances, the development of highly reactive tetrazines enabling quantitative elimination from trans‐cyclooctene linkers remains challenging. In this study, we present the synthesis and application of sulfo‐tetrazines, a class of derivatives featuring phenolic hydroxyl groups with increased acidity constants (pKa). This unique property leads to accelerated elimination and complete release of the caged molecules within minutes. Moreover, the inclusion of sulfonate groups provides a valuable synthetic handle, enabling further derivatization into sulfonamides, modified with diverse substituents. Significantly, we demonstrate the utility of sulfo‐tetrazines in efficiently activating fluorogenic compounds and prodrugs in living cells, offering exciting prospects for their application in bioorthogonal chemistry.

Bioorthogonal Chemistry

Tetrazine

Biocompatibility

Bioconjugation

Functional group

Cyclooctene

10.1002/anie.202411713

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Citations (1)

Synthesis of C₃-Substituted N1-tert-Butyl 1,2,4-Triazinium Salts via the Liebeskind–Srogl Reaction for Fluorogenic Labeling of Live Cells

The Journal of Organic Chemistry (2024)

Veronika Šlachtová Simona Bellová Milan Vrábel

We recently described the development and application of a new bioorthogonal conjugation, the triazinium ligation. To explore the wider application of this reaction, in this work, we introduce a general method for synthesizing C3-substituted triazinium salts based on the Liebeskind–Srogl cross-coupling reaction and catalytic thioether reduction. These methods enabled the synthesis of triazinium derivatives for investigating the effect of different substituents on the ligation kinetics and stability of the compounds under biologically relevant conditions. Finally, we demonstrate that the combination of a coumarin fluorophore attached to position C3 with a C5-(4-methoxyphenyl) substituent yields a fluorogenic triazinium probe suitable for no-wash, live-cell labeling. The developed methodology represents a promising synthetic approach to the late-stage modification of triazinium salts, potentially widening their applications in bioorthogonal reactions.

Bioorthogonal Chemistry

Thioether

10.1021/acs.joc.3c02454

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Citations (1)

Regio- and Diastereoselective 1,3-Dipolar Cycloadditions of 1,2,4-Triazin-1-ium Ylides: a Straightforward Synthetic Route to Polysubstituted Pyrrolo[2,1-f][1,2,4]triazines

ACS Omega (2022)

Juraj Galeta Veronika Šlachtová Martin Dračínský Milan Vrábel

A synthetic strategy to pyrrolo[2,1-f][1,2,4]triazines is reported. We show that various synthetically easily accessible 1,2,4-triazines can be efficiently alkylated under mild conditions to provide the corresponding 1-alkyl-1,2,4-triazinium salts. These bench-stable salts serve as precursors to triazinium ylides, which react in 1,3-dipolar cycloadditions with electron-poor dipolarophiles to yield polysubstituted pyrrolotriazines in a single step.

10.1021/acsomega.2c02276

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Citations (5)

Synthesis of C3-Substituted N1-tert-Butyl 1,2,4-Triazinium Salts via the Liebeskind–Srogl Reaction for Fluorogenic Labeling of Live Cells

Veronika Šlachtová Simona Bellová Milan Vrábel

We recently described the development and application of new bioorthogonal conjugation, the triazinium ligation. To explore the wider application of this reaction, in this work we introduce a general method for synthesizing C3-substituted triazinium salts based on the Liebeskind–Srogl cross-coupling reaction and catalytic thioether reduction. These methods enabled the synthesis of triazinium derivatives for investigating the effect of different substituents on the ligation kinetics and stability of the compounds under biologically relevant conditions. Finally, we demonstrate that the combination of coumarin fluorophore attached to position C3 with a C5-(4-methoxyphenyl) substituent, yields a fluorogenic triazinium probes suitable for no-wash, live-cell labeling. The developed methodology represents a promising synthetic approach to the late-stage modification of triazinium salts, potentially widening their application in bioorthogonal reactions.

Bioorthogonal Chemistry

Thioether

10.26434/chemrxiv-2023-lpf8m

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Citations (1)

Expanding the squaramide library as mycobacterial ATP synthase inhibitors: Innovative synthetic pathway and biological evaluation

Bioorganic & Medicinal Chemistry (2023)

Jan Chasák Lauren Oorts Milan Dak Veronika Šlachtová Václav Bazgier

10.1016/j.bmc.2023.117504

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Citations (3)

Triazinium Ligation: Bioorthogonal Reaction of N1‐Alkyl 1,2,4‐Triazinium Salts**

Angewandte Chemie International Edition (2023)

Veronika Šlachtová Simona Bellová Agustina La‐Venia Juraj Galeta Martin Dračínský

The development of reagents that can selectively react in complex biological media is an important challenge. Here we show that N1-alkylation of 1,2,4-triazines yields the corresponding triazinium salts, which are three orders of magnitude more reactive in reactions with strained alkynes than the parent 1,2,4-triazines. This powerful bioorthogonal ligation enables efficient modification of peptides and proteins. The positively charged N1-alkyl triazinium salts exhibit favorable cell permeability, which makes them superior for intracellular fluorescent labeling applications when compared to analogous 1,2,4,5-tetrazines. Due to their high reactivity, stability, synthetic accessibility and improved water solubility, the new ionic heterodienes represent a valuable addition to the repertoire of existing modern bioorthogonal reagents.

Bioorthogonal Chemistry

Reactivity

10.1002/anie.202306828

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Citations (16)

Benzoxazole Derivatives as Promising Antitubercular Agents

ChemistrySelect (2018)

Veronika Šlachtová Lucie Brulíková

Abstract Tuberculosis (TB) is an infectious disease caused predominantly by bacillus Mycobacterium tuberculosis (MTB) . The increasing prevalence of multidrug‐resistant MTB necessitates the discovery and development of alternative drugs against tuberculosis with a new mechanism of action. Over the past years, several benzoxazole derivatives have been synthesized and screened for their biological activity. Interestingly, some of them had promising antitubercular activity. Despite that, none of the benzoxazole derivatives has entered the phase of the preclinical hit‐to‐lead optimization step in anti‐TB research. In this review, we are summarizing recently published articles that evaluate the potency of benzoxazole heterocycle in the development of novel anti‐TB agents and outlined the future aspects of this promising heterocycle.

Benzoxazole

10.1002/slct.201800631

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Citations (44)

Bioorthogonal Chemistry in Cellular Organelles

Topics in Current Chemistry (2023)

Veronika Šlachtová Marek Chovanec Michal Rahm Milan Vrábel

Abstract While bioorthogonal reactions are routinely employed in living cells and organisms, their application within individual organelles remains limited. In this review, we highlight diverse examples of bioorthogonal reactions used to investigate the roles of biomolecules and biological processes as well as advanced imaging techniques within cellular organelles. These innovations hold great promise for therapeutic interventions in personalized medicine and precision therapies. We also address existing challenges related to the selectivity and trafficking of subcellular dynamics. Organelle-targeted bioorthogonal reactions have the potential to significantly advance our understanding of cellular organization and function, provide new pathways for basic research and clinical applications, and shape the direction of cell biology and medical research.

Bioorthogonal Chemistry

Organelle

Chemical Biology

Cell function

10.1007/s41061-023-00446-5

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Citations (6)

Novel thiazolidinedione-hydroxamates as inhibitors of Mycobacterium tuberculosis virulence factor Zmp1

European Journal of Medicinal Chemistry (2019)

Veronika Šlachtová Marek Šebela Eveline Torfs Lauren Oorts Davie Cappoen

Antimycobacterial

Thiazolidinedione

10.1016/j.ejmech.2019.111812

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Citations (19)

Triazinium Ligation: Bioorthogonal Reaction of N1‐Alkyl 1,2,4‐Triazinium Salts**

Angewandte Chemie (2023)

Veronika Šlachtová Simona Bellová Agustina La‐Venia Juraj Galeta Martin Dračínský

Abstract The development of reagents that can selectively react in complex biological media is an important challenge. Here we show that N 1‐alkylation of 1,2,4‐triazines yields the corresponding triazinium salts, which are three orders of magnitude more reactive in reactions with strained alkynes than the parent 1,2,4‐triazines. This powerful bioorthogonal ligation enables efficient modification of peptides and proteins. The positively charged N 1‐alkyl triazinium salts exhibit favorable cell permeability, which makes them superior for intracellular fluorescent labeling applications when compared to analogous 1,2,4,5‐tetrazines. Due to their high reactivity, stability, synthetic accessibility and improved water solubility, the new ionic heterodienes represent a valuable addition to the repertoire of existing modern bioorthogonal reagents.

Bioorthogonal Chemistry

Reactivity

Cell permeability

10.1002/ange.202306828

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Citations (2)