Video Experimental Relacionado

Updated: Jun 16, 2025

Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging

Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging

Published on: February 3, 2015

Descubrimiento de las tetrazinas monosubstituidas por diazol como herramientas bioortogonales óptimas

Yuxuan Li¹, Yeyu Su¹, Haoyu Wang¹

¹State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China.

Journal of the American Chemical Society

|August 21, 2024

Resumen

Las nuevas tetrazinas bioortogonales superan los límites de estabilidad y reactividad para el etiquetado biológico avanzado. Estas herramientas permiten el etiquetado ultrarrápido de proteínas en células y aplicaciones in vivo.

Área de la Ciencia:

Química bioortogonal
Biología química
Síntesis orgánica

Sus antecedentes:

Las tetrazinas monosubstituidas son herramientas bioortogonales vitales para la ligadura rápida con el transciclocteno.
Su uso en sistemas biológicos se ve obstaculizado por la paradoja reactividad-estabilidad.

Objetivo del estudio:

Para resolver la paradoja de la reactividad-estabilidad en las tetrazinas bioortogonales.
Descubrir nuevas tetrazinas con mayor estabilidad y reactividad para aplicaciones biológicas.

Principales métodos:

Cálculos teóricos para investigar los efectos estéricos sobre la reactividad y la estabilidad de la tetrazina.
Desarrollo de una ruta sintética para validar los resultados computacionales.
Codificación genética de aminoácidos no canónicos que contienen tetrazina en proteínas.
Experimentos de etiquetado bioortogonal in vitro e in vivo en células de mamíferos y ratones.

Principales resultados:

Descubrimiento de tetrazinas monosubstituidas de 1,3-azol-4-il y 1,2-azol-3-il con reactividad y estabilidad superiores.
La tetrazina más estable muestra una estabilidad del 71% después de 24 horas en medio de cultivo celular y una reactividad > 10^4 M^-1 s^-1.
Etiquetado de proteínas específicas del sitio en células vivas con velocidades ultra rápidas (> 10^7 M^-1 s^-1) utilizando tintes transciclocténicos fusionados con ciclopropano.
El éxito en el anclaje de proteínas en ratones vivos.

Conclusiones:

Los efectos estéricos son clave para resolver la paradoja de la reactividad-estabilidad de la tetrazina.
Las nuevas tetrazinas ofrecen herramientas reactivas bioortogonales óptimas para aplicaciones in vivo.
Estas tetrazinas permiten un etiquetado de proteínas bioortogonales sin precedentes en sistemas biológicos complejos.

Más Videos Relacionados

Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry

Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry

Published on: August 19, 2012

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry

Preparation and Evaluation of 99mTc-labeled Tridentate Chelates for Pre-targeting Using Bioorthogonal Chemistry

Published on: February 4, 2017

Videos de Conceptos Relacionados

Aryldiazonium Salts to Azo Dyes: Diazo Coupling

Aryldiazonium 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...

Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions

Diazonium 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...

Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1

Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic S_N1

Treating arylamines with nitrous acid gives aryldiazonium salts that are effective substrates in nucleophilic aromatic substitution reactions. The diazonio group in these salts can be easily displaced by different nucleophiles, yielding a wide variety of substituted benzenes. The leaving group departs as nitrogen gas, and this easy elimination is the driving force for the substitution reaction.
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo,...

Diazonium Group Substitution: –OH and –H

Diazonium Group Substitution: –OH and –H

Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

Carboxylic acids react with diazomethane in an ether solvent via alkylation at the carboxylate oxygen atom to give methyl esters of the corresponding acid with excellent yields.

1° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Mechanism

1° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO₂ Mechanism

Nitrous acid is a relatively weak and unstable acid prepared in situ by the reaction of sodium nitrite and cold, dilute hydrochloric acid. In an acidic solution, the nitrous acid undergoes protonation when it loses water to form a nitrosonium ion—an electrophile. Nitrous acid reacts with primary amines to give diazonium salts. The reaction is called diazotization of primary amines.