Open AccessArylethynyltrifluoroborate Dienophiles for on Demand Activation of IEDDA Reactions
Author(s) -
Zbigniew Zawada,
Zijian Guo,
Bruno L. Oliveira,
Claudio D. Navo,
Li He,
Pedro M. S. D. Cal,
Francisco Corzana,
Gonzalo JiménezOsés,
Gonçalo J. L. Bernardes
Publication year - 2021
Publication title -
bioconjugate chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.1c00276
Subject(s) - chemistry , cycloaddition , tetrazine , reactivity (psychology) , alkyne , combinatorial chemistry , organic chemistry , catalysis , medicine , alternative medicine , pathology
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 ( k 2 = 21 M -1 s -1 ) to no reaction with an alkyne-BF 3 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.