New insight into the molecular mechanism of protein cross-linking induced by cis-2-butene-1,4-dial, the metabolite of furan: Formation of 2-substituted pyrrole cross-links involving the cysteine and lysine residues

Muńko, Malwina; Ciesielska, Karolina; Pluskota-Karwatka, Donata

doi:10.1016/j.bioorg.2022.105852

Cited by 4 publications

(3 citation statements)

References 34 publications

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“…4 ). A similar observation for the formation of minor 2-thio N -pyrrole has also been reported previously 27 . Notably, less nucleophilic aromatic amines such as aniline also reacted with oxidized furan and 1-butanethiol to generate 3-thio N -pyrrole 2j in high yields (69.7%).…”

Section: Resultssupporting

confidence: 89%

Bioinspired one-pot furan-thiol-amine multicomponent reaction for making heterocycles and its applications

Wang,

Czabala,

Raj

2023

Nat Commun

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One-pot multicomponent coupling of different units in a chemoselective manner and their late-stage diversification has wide applicability in varying chemistry fields. Here, we report a simple multicomponent reaction inspired by enzymes that combines thiol and amine nucleophiles in one pot via a furan-based electrophile to generate stable pyrrole heterocycles independent of the diverse functionalities on furans, thiols and amines under physiological conditions. The resulting pyrrole provides a reactive handle to introduce diverse payloads. We demonstrate the application of Furan-Thiol-Amine (FuTine) reaction for the selective and irreversible labeling of peptides, synthesis of macrocyclic and stapled peptides, selective modification of twelve different proteins with varying payloads, homogeneous engineering of proteins, homogeneous stapling of proteins, dual modification of proteins with different fluorophores using the same chemistry and labeling of lysine and cysteine in a complex human proteome.

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Section: Resultssupporting

confidence: 89%

Bioinspired one-pot furan-thiol-amine multicomponent reaction for making heterocycles and its applications

Wang,

Czabala,

Raj

2023

Nat Commun

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“…Model systems used in scientific research are not always perfect, but they provide insight into similar events that may occur with biologically relevant molecules. Thus, the use of DOPE as a model amino acid cross-linking reagent in our earlier studies has shed new light on the reactivity of the furan metabolite (Muńko et al 2022 ). In the present work, this approach provides general, important data on the structural and mechanistic aspects of pyrrole cross-link formation.…”

Section: Discussionmentioning

confidence: 99%

“…Recently we showed that cis -2-butene-1,4-dial undergoes not only a major 1,4-, but also a minor 1,2-addition of a cysteine thiol group. Condensation of the minor adduct with the lysine derivatives yielded 1,2-substituted pyrroles (Muńko et al 2022 ). On the basis of their UV spectra and data obtained from LC–MS as well as LC–MS/MS analyses, we tentatively proposed structures of these newly identified cross-links, and we undertook studies aimed at their NMR characterisation.…”

Section: Introductionmentioning

confidence: 99%

Structural characterisation and pH-dependent preference of pyrrole cross-link isoforms from reactions of oxoenal with cysteine and lysine side chains as model systems

et al. 2023

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In this study, we subjected 5,5-diethoxy-4-oxopent-2-enal (DOPE), a model amino acids cross-linking reagent, to reactions with N-acetylcysteine (Ac-Cys) and Nα-acetyllysine (Ac-Lys), and identified three pyrrole cross-links. The compounds were isolated and their structures were rigorously determined by spectrometric and spectroscopic methods, including 2D NMR experiments. The use of 2D NMR spectroscopy was crucial to determine the position of the substituents in the pyrrole rings. The products were identified as 2,4-, 2,3-, and 2,5-substituted pyrroles. The data obtained from their structural characterisation can help similar studies on amino acids modifications induced by analogous bifunctional carbonyl compounds. Our results show that the study of pathways in which model electrophiles modify amino acids may be helpful for similar studies dealing with identification of structural changes in cysteine- and lysine-containing proteins associated with oxidative stress.

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Influence of furan and lead co-exposure at environmentally relevant concentrations on neurobehavioral performance, redox-regulatory system and apoptotic responses in rats

Owumi

Adedara

Otunla

et al. 2023

Environmental Toxicology and Pharmacology

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New insight into the molecular mechanism of protein cross-linking induced by cis-2-butene-1,4-dial, the metabolite of furan: Formation of 2-substituted pyrrole cross-links involving the cysteine and lysine residues

Cited by 4 publications

References 34 publications

Bioinspired one-pot furan-thiol-amine multicomponent reaction for making heterocycles and its applications

Bioinspired one-pot furan-thiol-amine multicomponent reaction for making heterocycles and its applications

Structural characterisation and pH-dependent preference of pyrrole cross-link isoforms from reactions of oxoenal with cysteine and lysine side chains as model systems

Influence of furan and lead co-exposure at environmentally relevant concentrations on neurobehavioral performance, redox-regulatory system and apoptotic responses in rats

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