Browse
Submit Data
Databases
API
Help

Dataset Information

32 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rapid Cu-free click chemistry with readily synthesized biarylazacyclooctynones.

ABSTRACT: Bioorthogonal chemical reactions, those that do not interact or interfere with biology, have allowed for exploration of numerous biological processes that were previously difficult to study. The reaction of azides with strained alkynes, such as cyclooctynes, readily forms a triazole product without the need for a toxic catalyst. Here we describe a biarylazacyclooctynone (BARAC) that has exceptional reaction kinetics and whose synthesis is designed to be both modular and scalable. We employed BARAC for live cell fluorescence imaging of azide-labeled glycans. The high signal-to-background ratio obtained using nanomolar concentrations of BARAC obviated the need for washing steps. Thus, BARAC is a promising reagent for in vivo imaging.

SUBMITTER: Jewett JC

PROVIDER: S-EPMC2840677 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Rapid Cu-free click chemistry with readily synthesized biarylazacyclooctynones.

Jewett John C JC Sletten Ellen M EM Bertozzi Carolyn R CR

Journal of the American Chemical Society 20100301 11

Bioorthogonal chemical reactions, those that do not interact or interfere with biology, have allowed for exploration of numerous biological processes that were previously difficult to study. The reaction of azides with strained alkynes, such as cyclooctynes, readily forms a triazole product without the need for a toxic catalyst. Here we describe a biarylazacyclooctynone (BARAC) that has exceptional reaction kinetics and whose synthesis is designed to be both modular and scalable. We employed BAR ...[more]

PMID: 20187640

Similar Datasets

A hydrophilic azacyclooctyne for Cu-free click chemistry.

Project description:Biomolecules labeled with azides can be detected through Cu-free click chemistry with cyclooctyne probes, but their intrinsic hydrophobicity can compromise bioavailability. Here, we report the synthesis and evaluation of a novel azacyclooctyne, 6,7-dimethoxyazacyclooct-4-yne (DIMAC). Generated in nine steps from a glucose analogue, DIMAC reacted with azide-labeled proteins and cells similarly to cyclooctynes. However, its superior polarity and water solubility reduced nonspecific binding, thereby improving the sensitivity of azide detection.

| S-EPMC2664610 | biostudies-literature

Strain-Promoted Catalyst-Free Click Chemistry for Rapid Construction of (64)Cu-Labeled PET Imaging Probes.

Project description:A rapid, efficient, and catalyst-free click chemistry method for the construction of (64)Cu-labeled PET imaging probes was reported based on the strain-promoted aza-dibenzocyclooctyne ligation. This new method was exemplified in the synthesis of (64)Cu-labeled RGD peptide for PET imaging of tumor integrin ?v?3 expression in vivo. The catalyst-free click chemistry reaction proceeded with a fast rate and eliminated the contamination problem of the catalyst Cu(I) ions interfering with the (64)Cu radiolabeling procedure under the conventional Cu-catalyzed 1,3-dipolar cycloaddition condition. The new strategy is simple and robust, and the resultant (64)Cu-labeled RGD probe was obtained in an excellent yield and high specific activity. PET imaging and biodistribution studies revealed significant, specific uptake of the "click" (64)Cu-labeled RGD probe in integrin ?v?3-positive U87MG xenografts with little uptake in nontarget tissues. This new approach is versatile, which warrants a wide range of applications for highly diverse radiometalated bioconjugates for radioimaging and radiotherapy.

| S-EPMC4025793 | biostudies-other

Synthesis of a fluorogenic cyclooctyne activated by Cu-free click chemistry.

Project description:Cyclooctyne-based probes that become fluorescent upon reaction with azides are important targets for real-time imaging of azide-labeled biomolecules. The concise synthesis of a coumarin-conjugated cyclooctyne, coumBARAC, that undergoes a 10-fold enhancement in fluorescence quantum yield upon triazole formation with organic azides is reported. The design principles embodied in coumBARAC establish a platform for generating fluorogenic cyclooctynes suited for biological imaging.

| S-EPMC3219546 | biostudies-literature

Thiacycloalkynes for copper-free click chemistry.

Project description: Not available

| S-EPMC3384729 | biostudies-literature

Novel Liposomal Azido Mannosamine Lipids on Metabolic Cell Labeling and Imaging via Cu-Free Click Chemistry.

Project description:In comparison with the popular Ac4ManNAz applied as cell labels via Cu-free click chemistry, two novel azido mannosamine lipids with C6 and C12 esters on anomeric hydroxyl groups were prepared and encapsulated in a liposome delivery system, which enhanced chemical stabilities and showed good cell-metabolizable labeling efficiency on MDA-MB-231 cells with strong fluorescence after the treatment of DBCO-Cy5 by triazole formation via click chemistry.

| S-EPMC7470023 | biostudies-literature

Copper-free click chemistry in living animals.

Project description:Chemical reactions that enable selective biomolecule labeling in living organisms offer a means to probe biological processes in vivo. Very few reactions possess the requisite bioorthogonality, and, among these, only the Staudinger ligation between azides and triarylphosphines has been employed for direct covalent modification of biomolecules with probes in the mouse, an important model organism for studies of human disease. Here we explore an alternative bioorthogonal reaction, the 1,3-dipolar cycloaddition of azides and cyclooctynes, also known as "Cu-free click chemistry," for labeling biomolecules in live mice. Mice were administered peracetylated N-azidoacetylmannosamine (Ac(4)ManNAz) to metabolically label cell-surface sialic acids with azides. After subsequent injection with cyclooctyne reagents, glycoconjugate labeling was observed on isolated splenocytes and in a variety of tissues including the intestines, heart, and liver, with no apparent toxicity. The cyclooctynes tested displayed various labeling efficiencies that likely reflect the combined influence of intrinsic reactivity and bioavailability. These studies establish Cu-free click chemistry as a bioorthogonal reaction that can be executed in the physiologically relevant context of a mouse.

| S-EPMC2836626 | biostudies-literature

Reactivity of biarylazacyclooctynones in copper-free click chemistry.

Project description:The 1,3-dipolar cycloaddition of cyclooctynes with azides, also called "copper-free click chemistry", is a bioorthogonal reaction with widespread applications in biological discovery. The kinetics of this reaction are of paramount importance for studies of dynamic processes, particularly in living subjects. Here we performed a systematic analysis of the effects of strain and electronics on the reactivity of cyclooctynes with azides through both experimental measurements and computational studies using a density functional theory (DFT) distortion/interaction transition state model. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. We found that substituents on BARAC's aryl rings can alter the calculated transition state interaction energy of the cycloaddition through electronic effects or the calculated distortion energy through steric effects. Experimental data confirmed that electronic perturbation of BARAC's aryl rings has a modest effect on reaction rate, whereas steric hindrance in the transition state can significantly retard the reaction. Drawing on these results, we analyzed the relationship between alkyne bond angles, which we determined using X-ray crystallography, and reactivity, quantified by experimental second-order rate constants, for a range of cyclooctynes. Our results suggest a correlation between decreased alkyne bond angle and increased cyclooctyne reactivity. Finally, we obtained structural and computational data that revealed the relationship between the conformation of BARAC's central lactam and compound reactivity. Collectively, these results indicate that the distortion/interaction model combined with bond angle analysis will enable predictions of cyclooctyne reactivity and the rational design of new reagents for copper-free click chemistry.

| S-EPMC3368396 | biostudies-literature

Sonochemically Synthesized Spin-Canted CuFe2O4 Nanoparticles for Heterogeneous Green Catalytic Click Chemistry.

Project description:Heterogeneous green catalysis by using magnetically separable nanometal-oxide catalysts has become a subject of prime focus recently. PXRD (powder X-ray diffraction), FESEM (field emission scanning electron microscopy), and HRTEM (high-resolution tunneling electron microscopy) with IR and Raman spectroscopy are applied to analyze the structural and microstructural properties of nanosized (?15.3 nm) CuFe2O4 synthesized by both sonochemical and mechanochemical processes. The sonochemical process provides a better uniformity of sizes of the nanoparticles (NPs). Rietveld refinement with the PXRD pattern reveals the inverse spinel-like architecture of CuFe2O4 NPs. The Raman spectra also indicate the phase purity of the synthesized material. The static magnetic measurements are performed at different magnetic fields and temperature ranges from 300 to 5 K, which confirms the existence of the ferrimagnetic phase mixed with some finer superparamagnetic (SPM) nanophases within the sample. Unsaturated magnetization is observed even at an applied 5 T magnetic field for the presence of spin-canting nature in the partially inverted copper ferrite phases at the surfaces of the nanoparticles. Now, these coupled magnetic CuFe2O4 NPs are used as a heterogeneous catalyst for three-component Huisgen 1,3-dipolar cycloaddition click reaction in aqueous media. By this catalyst system, we were able to couple alkyl halide, epoxide, or boronic acid with alkynes efficiently to furnish 1,4-disubstituted 1,2,3-triazoles in excellent yields within very short reaction time. The test for heterogeneity, reusability, and reproducibility of the catalyst has also been performed successfully without prominent decrease in yield up to the fifth cycle.

| S-EPMC6714523 | biostudies-literature

A DOTA-peptide conjugate by copper-free click chemistry.

Project description:Attachment of DOTA to a novel monofluoro-cyclooctyne facilitates bioconjugation to an azide-modified peptide via Cu-free click chemistry. The resulting conjugate was radiolabeled with (111)In to afford a potential targeted molecular imaging agent with high specific activity and an excellent radiochemical purity.

| S-EPMC3774834 | biostudies-literature

Copper-free click chemistry for dynamic in vivo imaging.

Project description:Dynamic imaging of proteins in live cells is routinely performed by using genetically encoded reporters, an approach that cannot be extended to other classes of biomolecules such as glycans and lipids. Here, we report a Cu-free variant of click chemistry that can label these biomolecules rapidly and selectively in living systems, overcoming the intrinsic toxicity of the canonical Cu-catalyzed reaction. The critical reagent, a substituted cyclooctyne, possesses ring strain and electron-withdrawing fluorine substituents that together promote the [3 + 2] dipolar cycloaddition with azides installed metabolically into biomolecules. This Cu-free click reaction possesses comparable kinetics to the Cu-catalyzed reaction and proceeds within minutes on live cells with no apparent toxicity. With this technique, we studied the dynamics of glycan trafficking and identified a population of sialoglycoconjugates with unexpectedly rapid internalization kinetics.

| S-EPMC2040404 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data