| Bioorthogonal chemistry enables biological chemists to study the dynamics of complex biological systems. Bioorthogonal chemistry allows the selective reaction of an orthogonal tag, which is incorporated on the molecule of interest via biosynthetic or biochemical pathway, and its reactive partner without interfering with native biochemical processes. A number of reactions have been developed in the past two decades. However, there is still a need to develop new chemistries to widen the scope and power of these chemistries to elucidate the biological systems. Therefore, we developed a metal-free bioorthogonal reaction between N-hydroxylamine (orthogonal tag) and a bifunctional probe with aldehyde and alkene (reactive partner) to form a stable isoxazolidine cycloadduct. We showed that glucose could be modified with N-hydroxylamine in four steps. In addition, we designed and synthesized probes that condense then cyclize at 37 °C within 24 hours to yield the cycloadduct, thus making this reaction a viable chemistry to use in biological systems. |
