Related Experiment Video
Updated: May 29, 2026
09:35
Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units
Published on: September 18, 2016
Sulfated ligands for the copper(I)-catalyzed azide-alkyne cycloaddition
Wei Wang1, Senglian Hong, Andrew Tran
1Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Chemistry, an Asian Journal
|September 10, 2011
Summary
Two new ligands, BTTP and BTTPS, were compared for copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) bioconjugation. BTTPS-copper(I) is superior for live-cell labeling due to reduced cellular copper uptake.
Area of Science:
- Bioconjugation Chemistry
- Catalysis
- Molecular Biology
Background:
- Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is a key reaction in click chemistry.
- Tris(triazolylmethyl)amine ligands accelerate CuAAC reactions.
- Developing efficient ligands is crucial for bioconjugation applications.
Purpose of the Study:
- To compare the efficacy of two novel tris(triazolylmethyl)amine ligands, BTTP and BTTPS, in CuAAC reactions.
- To evaluate their performance in various bioconjugation scenarios, including labeling glycoproteins and bacterial surface proteins.
- To assess their suitability for live-cell applications.
Main Methods:
- Synthesis and characterization of BTTP and BTTPS ligands.
- In vitro kinetic studies of CuAAC reactions catalyzed by BTTP-Cu(I) and BTTPS-Cu(I).
- Bioconjugation experiments involving alkyne-tagged glycoproteins in cell lysates, surface labeling of glycoproteins on live mammalian cells, and labeling of surface proteins on live Escherichia coli.
Main Results:
- BTTPS demonstrated faster kinetics than BTTP in in vitro CuAAC reactions.
- BTTP showed higher labeling efficiency for negatively charged biomolecules due to less electrostatic repulsion.
- BTTPS-Cu(I) exhibited reduced cellular internalization of copper, making it advantageous for live-cell labeling.
Conclusions:
- Both BTTP and BTTPS are effective ligands for CuAAC reactions in bioconjugation.
- BTTPS-Cu(I) is a preferred system for live-cell labeling due to its minimized cellular copper uptake.
- Ligand design, considering factors like charge and cellular interactions, is critical for optimizing bioconjugation strategies.
Related Concept Videos
02:26Preparation and Reactions of Sulfides
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
02:51Metal-Ligand Bonds
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
01:22Preparation of 1° Amines: Azide Synthesis
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
01:20Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...
01:16Cycloaddition Reactions: Overview
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
01:11Aryldiazonium Salts to Azo Dyes: Diazo Coupling
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the para position.