Arylethynyltrifluoroborate Dienophiles for on Demand Activation of IEDDA Reactions

Overview

Journal Bioconjug Chem

Publisher American Chemical Society

Specialty Biochemistry

Date 2021 Jul 15

PMID 34264651

Citations 2

Authors

Zbigniew Zawada

Zijian Guo

Bruno L Oliveira

Claudio D Navo

He Li

Pedro M S D Cal

Francisco Corzana

Gonzalo Jimenez-Oses

Goncalo J L Bernardes

Affiliations

Soon will be listed here.

Abstract

Strained alkenes and alkynes are the predominant dienophiles used in inverse electron demand Diels-Alder (IEDDA) reactions. However, their instability, cross-reactivity, and accessibility are problematic. Unstrained dienophiles, although physiologically stable and synthetically accessible, react with tetrazines significantly slower relative to strained variants. Here we report the development of potassium arylethynyltrifluoroborates as unstrained dienophiles for fast, chemically triggered IEDDA reactions. By varying the substituents on the tetrazine (e.g., pyridyl- to benzyl-substituents), cycloaddition kinetics can vary from fast ( = 21 M s) to no reaction with an alkyne-BF dienophile. The reported system was applied to protein labeling both in the test tube and fixed cells and even enabled mutually orthogonal labeling of two distinct proteins.

Citing Articles

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Alkynone β-trifluoroborates: A new class of amine-specific biocompatible click reagents.

Teng S, Ng E, Zhang Z, Soon C, Xu H, Li R Sci Adv. 2023; 9(17):eadg4924.

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