Dataset Information

Alkyne Ligation Handles: Propargylation of Hydroxyl, Sulfhydryl, Amino, and Carboxyl Groups via the Nicholas Reaction.

ABSTRACT: The Nicholas reaction has been applied to the installation of alkyne ligation handles. Acid-promoted propargylation of hydroxyl, sulfhydryl, amino, and carboxyl groups using dicobalt hexacarbonyl-stabilized propargylium ions is reported. This method is useful for introduction of propargyl groups into base-sensitive molecules, thereby expanding the toolbox of methods for the incorporation of alkynes for bio-orthogonal reactions. High-value molecules are used as the limiting reagent, and various propargylium ion precursors are compared.

SUBMITTER: Wells SM

PROVIDER: S-EPMC5234733 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Alkyne Ligation Handles: Propargylation of Hydroxyl, Sulfhydryl, Amino, and Carboxyl Groups via the Nicholas Reaction.

Wells Sarah M SM Widen John C JC Harki Daniel A DA Brummond Kay M KM

Organic letters 20160829 18

The Nicholas reaction has been applied to the installation of alkyne ligation handles. Acid-promoted propargylation of hydroxyl, sulfhydryl, amino, and carboxyl groups using dicobalt hexacarbonyl-stabilized propargylium ions is reported. This method is useful for introduction of propargyl groups into base-sensitive molecules, thereby expanding the toolbox of methods for the incorporation of alkynes for bio-orthogonal reactions. High-value molecules are used as the limiting reagent, and various p ...[more]

PMID: 27570975

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Project description:The present study addresses existing data on the affinity and conjugation of sulfhydryl (thiol; -SH) groups of low- and high-molecular-weight biological ligands with mercury (Hg). The consequences of these interactions with special emphasis on pathways of Hg toxicity are highlighted. Cysteine (Cys) is considered the primary target of Hg, and link its sensitivity with thiol groups and cellular damage. In vivo, Hg complexes play a key role in Hg metabolism. Due to the increased affinity of Hg to SH groups in Cys residues, glutathione (GSH) is reactive. The geometry of Hg(II) glutathionates is less understood than that with Cys. Both Cys and GSH Hg-conjugates are important in Hg transport. The binding of Hg to Cys mediates multiple toxic effects of Hg, especially inhibitory effects on enzymes and other proteins that contain free Cys residues. In blood plasma, albumin is the main Hg-binding (Hg2+, CH3Hg+, C2H5Hg+, C6H5Hg+) protein. At the Cys34 residue, Hg2+ binds to albumin, whereas other metals likely are bound at the N-terminal site and multi-metal binding sites. In addition to albumin, Hg binds to multiple Cys-containing enzymes (including manganese-superoxide dismutase (Mn-SOD), arginase I, sorbitol dehydrogenase, and δ-aminolevulinate dehydratase, etc.) involved in multiple processes. The affinity of Hg for thiol groups may also underlie the pathways of Hg toxicity. In particular, Hg-SH may contribute to apoptosis modulation by interfering with Akt/CREB, Keap1/Nrf2, NF-κB, and mitochondrial pathways. Mercury-induced oxidative stress may ensue from Cys-Hg binding and inhibition of Mn-SOD (Cys196), thioredoxin reductase (TrxR) (Cys497) activity, as well as limiting GSH (GS-HgCH3) and Trx (Cys32, 35, 62, 65, 73) availability. Moreover, Hg-thiol interaction also is crucial in the neurotoxicity of Hg by modulating the cytoskeleton and neuronal receptors, to name a few. However, existing data on the role of Hg-SH binding in the Hg toxicity remains poorly defined. Therefore, more research is needed to understand better the role of Hg-thiol binding in the molecular pathways of Hg toxicology and the critical role of thiols to counteract negative effects of Hg overload.

Dataset Information

Alkyne Ligation Handles: Propargylation of Hydroxyl, Sulfhydryl, Amino, and Carboxyl Groups via the Nicholas Reaction.

Publications

Alkyne Ligation Handles: Propargylation of Hydroxyl, Sulfhydryl, Amino, and Carboxyl Groups via the Nicholas Reaction.

Similar Datasets

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