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Showing papers on "Click chemistry published in 2003"


Journal ArticleDOI
TL;DR: The copper-(I)-catalyzed 1,2,3-triazole formation from azides and terminal acetylenes is a particularly powerful linking reaction, due to its high degree of dependability, complete specificity, and the bio-compatibility of the reactants.

2,882 citations


Journal ArticleDOI
TL;DR: It is shown that several enzymes can be labeled in an activity-based manner both in vitro and in vivo by an azido-sulfonate ester probe and that these labeling events can be detected in whole proteomes by copper-catalyzed ligation with a rhodamine-alkyne reagent.
Abstract: Toward the goal of assigning function to the tens of thousands of protein products encoded by eukaryotic and prokaryotic genomes, the field of proteomics requires new technologies that can functionally characterize proteins within the dynamic environment of the cell, where these biomolecules are subject to myriad posttranslational modifications and the actions of endogenous activators and inhibitors. Here, we report an advanced strategy for activity-based protein profiling (ABPP) that addresses this important need. We show that several enzymes can be labeled in an activity-based manner both in vitro and in vivo by an azido-sulfonate ester probe and that these labeling events can be detected in whole proteomes by copper-catalyzed ligation with a rhodamine-alkyne reagent. This click chemistry-based strategy for ABPP represents a unique and versatile method for functional proteome analysis.

919 citations


Journal ArticleDOI
TL;DR: The problems of weak substrate affinity and low catalytic proficiency of fucosyltransferase was offset by recruiting additional binding features, in this case hydrophobic interactions, to produce a high affinity inhibitor, 24, with Ki = 62 nM.
Abstract: Potent inhibitors of fucosyltransferases, and glycosyltransferases in general, have been elusive due to the inherent barriers surrounding the family of glycosyltransfer reactions. The problems of weak substrate affinity and low catalytic proficiency of fucosyltransferase was offset by recruiting additional binding features, in this case hydrophobic interactions, to produce a high affinity inhibitor, 24, with Ki = 62 nM. The molecule was identified from a GDP-triazole library of 85 compounds, which was produced by the Cu(I)-catalyzed [2 + 3] cycloaddition reaction between azide and acetylene reactants, followed by in situ screening without product isolation.

416 citations


Patent
30 May 2003
TL;DR: In this article, a copper catalyzed click chemistry ligation process is employed to bind azides and terminal acetylenes to provide 1,4-disubstituted 1,2,3-triazole triazoles.
Abstract: A copper catalyzed click chemistry ligation process is employed to bind azides and terminal acetylenes to provide 1,4-disubstituted 1,2,3-triazole triazoles. The process comprises contacting an organic azide and a terminal alkyne with a source of reactive Cu(I) ion for a time sufficient to form by cycloaddition a 1,4-disubstituted 1,2,3-triazole. The source of reactive Cu(I) ion can be, for example, a Cu(I) salt or copper metal. The process is preferably carried out in a solvent, such as an aqueous alcohol. Optionally, the process can be performed in a solvent that comprises a ligand for Cu(I) and an amine.

283 citations


Journal ArticleDOI
TL;DR: The FAM-labeled ssDNA was successfully used as a primer to produce DNA sequencing products with single-base resolution in a capillary electrophoresis DNA sequencer with laser-induced fluorescence detection.
Abstract: “Click chemistry” 1,3-dipolar cycloaddition between alkynyl 6-carboxyfluorescein (FAM) and azido-labeled single-stranded (ss) DNA was carried out under aqueous conditions to produce FAM-labeled ssDNA in quantitative yield. The FAM-labeled ssDNA was successfully used as a primer to produce DNA sequencing products with single-base resolution in a capillary electrophoresis DNA sequencer with laser-induced fluorescence detection.

260 citations