Diazo group as a new chemical reporter for bioorthogonal labelling of biomolecules

Josa-Culleré, Laia; Wainman, Yéléna A.; Brindle, Kevin M.; Leeper, Finian J.

doi:10.1039/c4ra08861a

Cited by 19 publications

(20 citation statements)

References 30 publications

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“…92,109 (B) Labeling of a diazo-modified lysozyme with a cyclooctyne. 93 (C) Labeling of a metabolized diazo sugar displayed on the surface of human cells with a cyclooctyne. 92 …”

Section: Figurementioning

confidence: 99%

Diazo Compounds: Versatile Tools for Chemical Biology

2016

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Diazo groups have broad and tunable reactivity. That and other attributes endow diazo compounds with the potential to be valuable reagents for chemical biologists. The presence of diazo groups in natural products underscores their metabolic stability and anticipates their utility in a biological context. The chemoselectivity of diazo groups, even in the presence of azido groups, presents many opportunities. Already, diazo compounds have served as chemical probes and elicited novel modifications of proteins and nucleic acids. Here, we review advances that have facilitated the chemical synthesis of diazo compounds, and we highlight applications of diazo compounds in the detection and modification of biomolecules.

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“…92,109 (B) Labeling of a diazo-modified lysozyme with a cyclooctyne. 93 (C) Labeling of a metabolized diazo sugar displayed on the surface of human cells with a cyclooctyne. 92 …”

Section: Figurementioning

confidence: 99%

Diazo Compounds: Versatile Tools for Chemical Biology

2016

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“…A complement to azido groups, diazo groups have been employed in many biochemical applications, including reversible 1 and non-reversible protein alkylations, 2 nucleic acid conjugation, 3 and other bioconjugations. 4 Extant strategies to install pendant diazo groups 5 and to prepare them directly by deimidogenation of a parent azide 6 facilitate their use.…”

Section: Introductionmentioning

confidence: 99%

Rapid cycloaddition of a diazo group with an unstrained dipolarophile

Aronoff

Gold

Raines

2016

Tetrahedron Letters

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The cycloaddition of a diazoacetamide with ethyl 4,4,4-trifluorocrotonate proceeds with k = 0.1 M−1s−1. This second-order rate constant rivals those of optimized strain-promoted azide– alkyne cycloadditions, even though the reaction does not release strain. The regioselectivity and a computational distortion/interaction analysis of the reaction energetics are consistent with the formation of an N–H…F–C hydrogen bond in the transition state and the electronic character of the trifluorocrotonate. Analogous reactions with an azidoacetamide dipole or with an acrylate or crotonate dipolarophile were much slower. These findings suggest a new strategy for the design of diazo-selective reagents for chemical biology.

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“…Such cyclic dehydroalanine derivatives are highly electrophilic and can quickly react in situ with silyl enol ethers, diazo compounds and dienes under very mild conditions at room temperature, and in the absence of metal catalysts without the need for ring strain activation. In view of the growing interest in diazo groups as new chemical reporters for bioorthogonal labelling of biomolecules and versatile tools for chemical biology we believe that our methodology offers potential for bioconjugation and post‐translational modification of proteins under controlled physiological conditions, although the low stability of MPO derivatives in water currently limits their biological scope. This possibility, together with the scope to extend our methodology to serine residues within a peptide context to chemically install MIO‐type modifications, are currently being evaluated in our laboratory.…”

Section: Figurementioning

confidence: 99%

Elusive Dehydroalanine Derivatives with Enhanced Reactivity

et al. 2019

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For the first time, a simple methodology for the chemical synthesis and use of highly reactive 4‐methylenoxazol‐5(4H)‐ones from serine is presented. These dehydroalanine derivatives, which resemble the natural 4‐methylidenimidazole‐5‐one (MIO) cofactor present in lyases and aminomutases, undergo rapid reaction with carbon nucleophiles such as silyl enol ethers, as well as cycloaddition reactions with diazo compounds and reactive dienes, under very mild conditions and without any need for metal catalysts or ring‐strain activation, offering potential for bioconjugation.

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Diazo group as a new chemical reporter for bioorthogonal labelling of biomolecules

Abstract: Diazoacetyl groups undergo spontaneous cycloaddition with strained alkenes and alkynes and can be bioorthogonal reporter groups labelling proteins and glycans.

Cited by 19 publications

References 30 publications

Diazo Compounds: Versatile Tools for Chemical Biology

Diazo Compounds: Versatile Tools for Chemical Biology

Rapid cycloaddition of a diazo group with an unstrained dipolarophile

Elusive Dehydroalanine Derivatives with Enhanced Reactivity

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