Affiliation:
1. Institute of Organic Chemistry and Biochemistry of the CAS Flemingovo nám. 2 16000 Prague Czech Republic
2. Current address: Instituto de Química Rosario Facultad de Ciencias Bioquímicas y Farmacéuticas Universidad Nacional de Rosario-CONICET Suipacha 531 S2002LRK Rosario Argentina
Abstract
AbstractThe development of reagents that can selectively react in complex biological media is an important challenge. Here we show that N1‐alkylation of 1,2,4‐triazines yields the corresponding triazinium salts, which are three orders of magnitude more reactive in reactions with strained alkynes than the parent 1,2,4‐triazines. This powerful bioorthogonal ligation enables efficient modification of peptides and proteins. The positively charged N1‐alkyl triazinium salts exhibit favorable cell permeability, which makes them superior for intracellular fluorescent labeling applications when compared to analogous 1,2,4,5‐tetrazines. Due to their high reactivity, stability, synthetic accessibility and improved water solubility, the new ionic heterodienes represent a valuable addition to the repertoire of existing modern bioorthogonal reagents.
Funder
Ústav organické chemie a biochemie Akademie věd České republiky
Grantová Agentura České Republiky
Ministerstvo Školství, Mládeže a Tělovýchovy