The discovery of pyridinium 1,2,4-triazines with enhanced performance in bioconjugation reactions

Chemical Science
Sebastian J SieglMilan Vrabel

Abstract

1,2,4-Triazines have recently been identified as versatile dienes participating in the inverse electron-demand Diels-Alder reaction with strained dienophiles. However, their widespread utility in bioconjugation reactions is still limited. Herein, we report a systematic study on the reactivity of various 1,2,4-triazines with trans-cyclooctenes showing that the structure of both the triazine and the dienophile significantly affect the reaction rate. Our kinetic study led to the discovery of novel cationic 1,2,4-triazines with superior properties for bioconjugation reactions. We have developed an efficient method that enables their late-stage functionalization and allows for easy access to various useful heterobifunctional scaffolds. In addition, these charged dienes form unprecedented fluorescent products upon reaction with trans-cyclooctenes and can be used for fluorogenic labeling of subcellular compartments in live cells.

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Citations

Dec 19, 2018·Chembiochem : a European Journal of Chemical Biology·Sebastian J SieglMilan Vrabel
Apr 18, 2019·Organic & Biomolecular Chemistry·Longhuai ChengZhen Xi
Apr 28, 2020·Chemistry : a European Journal·Juraj GaletaMilan Vrabel
Jan 8, 2020·Chemical Science·David N KamberJennifer A Prescher
Dec 16, 2017·Chemistry : a European Journal·Sebastian J SieglMilan Vrabel
Nov 6, 2020·Current Opinion in Chemical Biology·Mike L W J SmeenkKimberly M Bonger
Mar 1, 2020·Israel Journal of Chemistry·Jessica E Pigga, Joseph M Fox
Jan 1, 2020·Nature Reviews. Chemistry·Sean S Nguyen, Jennifer A Prescher
Jul 15, 2021·Chembiochem : a European Journal of Chemical Biology·Yun Hu, Jennifer M Schomaker
Jul 2, 2021·Bioconjugate Chemistry·Aaditya Govindarajan, Vasuki Gnanasambandam
Jul 25, 2018·Chemical Reviews·Christopher D SpicerMolly M Stevens
May 5, 2018·Accounts of Chemical Research·R David Row, Jennifer A Prescher
Nov 25, 2017·The Journal of Organic Chemistry·Jessica G K O'BrienJoseph M Fox
Apr 21, 2018·ACS Chemical Biology·Qi ZhangEvripidis Gavathiotis
Sep 30, 2021·Chemical Reviews·Fa-Guang ZhangJun-An Ma

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Methods Mentioned

BETA
NMR
Fluorescence

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