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

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.

SUBMITTER: Siegl SJ

PROVIDER: S-EPMC6092722 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Siegl Sebastian J SJ Dzijak Rastislav R Vázquez Arcadio A Pohl Radek R Vrabel Milan M

Chemical science 20170301 5

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 <i>trans</i>-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 ...[more]

PMID: 30155204

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