Mechanistic Investigation of the Staudinger Ligation

Lin, Fiona L.; Hoyt, Helen M.; Halbeek, Herman van; Bergman, Robert G.; Bertozzi, Carolyn R.

doi:10.1021/ja044461m

Cited by 335 publications

(308 citation statements)

References 22 publications

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“…The azide is well-suited as a chemical reporter because it adds a small structural perturbation to the underlying sugar, is essentially inert to the cellular environment, and has multiple modes of reactivity (8). The Staudinger ligation, which capitalizes on the electrophilic character of the azide, chemoselectively forms an amide bond between azides and triarylphosphines (9). This reaction has been employed to tag azidosugar-labeled glycoconjugates on cultured cells and in live mice (10,11).…”

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confidence: 99%

Copper-free click chemistry in living animals

Chang

Prescher²,

Sletten³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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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 (Ac4ManNAz) 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.

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confidence: 99%

Copper-free click chemistry in living animals

Chang

Prescher²,

Sletten³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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580

506

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“…These advantages, along with the chemoselectivity of the reaction, have resulted in extensive use of the Staudinger ligation for labeling biomolecules [11] . Despite its effectiveness, the Staudinger ligation is limited by its relatively slow reaction kinetics and susceptibility to phosphine oxidation [11,12] .…”

Section: History Of Developmentmentioning

confidence: 99%

Bioorthogonal chemistries for nanomaterial conjugation and targeting

Rahim

Kota

Lee

et al. 2013

Nanotechnology Reviews

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Bioorthogonal chemistries are covalent reaction pairs that proceed in the presence of biological components with complete specificity. A suite of reactions has been described to date that provides scientists and engineers with diverse operational characteristics for different applications. Nanomaterials in particular have benefitted from these new capabilities, resulting in improved coupling efficiencies and multifunctionality. In this review, we will discuss the application of bioorthogonal chemistries to different nanomaterial systems, highlighting the advantages and limitations for use in bioconjugation. We will also describe how recent improvements in the reaction speed of catalyst-free bioorthogonal chemistries have enabled the successful coupling of nanomaterials directly to live cells. Using a recently developed reaction pair, tetrazine and trans -cyclooctene, the direct covalent coupling to cells has been shown to occur on time-scales that are relevant for biological studies and diagnostic applications and can even amplify nanomaterial binding greater than tenfold relative to traditional immunoconjugates. This powerful technique still maintains exquisite specificity, however, yielding robust results in clinical diagnostic applications using human tissue and blood samples. Future work will likely focus on further advancement of the in situ amplification technique, such as increasing nanomaterial binding, enabling multiplexed detection through the use of orthogonal reaction systems and extension to applications in vivo .

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“…In the past, NMR was used to study the mechanism and the reaction rate of the Staudinger ligation [34,35], but costly 13 C-labeled starting materials were used to quantitatively determine the spectra in a reasonable time span. To avoid performing circumstantial syntheses for the preparation of the 13 C-enriched starting materials and/or long-lasting measurements, we focused on the application of 19 F NMR, since 19 F-containing derivatives were mandatory to prepare as reference compounds for the identification of the corresponding 18 F radiotracers and, therefore, they were already available [36].…”

Section: Introductionmentioning

confidence: 99%

Structural and Kinetic Considerations for the Application of the Traceless Staudinger Ligation to Future ¹⁸F Radiolabeling Using XRD and ¹⁹F NMR

Köckerling

Mamat

2017

Int J of Chemical Kinetics

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A 4-fluorobenzoate-functionalized phosphane was synthesized and reacted with different azides using the traceless Staudinger ligation as a representative sample reaction for future radiolabeling purposes with short-lived radionuclides like fluorine-18. For this purpose, the reaction rate was evaluated at different temperatures. The effect of starting material concentrations and the influence of the steric effect coming from the applied azides were investigated. 19 F NMR was used to determine the reaction half-live (τ 1/2 ) and the reaction rate constant (k obs ) of this ligation under mild reaction conditions in a water-acetonitrile mixture. Furthermore, the phosphane key compound 1 (orthorhombic, space group Pna2 1 , a = 18.6363(9), b = 8.3589(4), c = 18.5480(9)Å, V = 2889.4(2)Å 3 , Z = 8, D obs = 1.277 g/cm 3 ), which acts as starting material for all subsequent syntheses, and the fluorine-containing phosphane 3 (monoclinic, space group P2 1 /c, a = 8.321(2), b = 16.160(4), c = 14.940(4)Å, β = 99.51(1)°, V = 1981.4(8)Å 3 , Z = 4, D obs = 1.342 g/cm 3 ) were analyzed by single-crystal XRD.

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Mechanistic Investigation of the Staudinger Ligation

Cited by 335 publications

References 22 publications

Copper-free click chemistry in living animals

Copper-free click chemistry in living animals

Bioorthogonal chemistries for nanomaterial conjugation and targeting

Structural and Kinetic Considerations for the Application of the Traceless Staudinger Ligation to Future ¹⁸F Radiolabeling Using XRD and ¹⁹F NMR

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Mechanistic Investigation of the Staudinger Ligation

Cited by 335 publications

References 22 publications

Copper-free click chemistry in living animals

Copper-free click chemistry in living animals

Bioorthogonal chemistries for nanomaterial conjugation and targeting

Structural and Kinetic Considerations for the Application of the Traceless Staudinger Ligation to Future 18F Radiolabeling Using XRD and 19F NMR

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Structural and Kinetic Considerations for the Application of the Traceless Staudinger Ligation to Future ¹⁸F Radiolabeling Using XRD and ¹⁹F NMR