Date of this Version
University of Nebraska-Lincoln Research Fair, Lincoln, Nebraska, April 2016.
Click chemistry describes crosslinking reactions in which pairs of functional groups selectively “click” together to form linkages. The idea of our project is to explore the use of cyclobutene-containing fatty acids as a new class of “click” reagents as a tool for protein modification.
There is great interest in performing click reactions under biologically relevant conditions, in the presence of cells, and even within cells. The best known click reaction, the cycloaddition of alkynes and azides, is highly specific, can be conducted in the presence of buffers and proteins, and forms stable cycloadducts. However, use in biological systems is limited by the need to employ a toxic copper catalyst to achieve useful reaction rates. A number of approaches have been investigated to achieve fast click reactions that do not require a catalyst (Bertozzi 2015).
The cycloaddition of 1,2,4,5-tetrazines with strained alkenes has emerged as an effective alternative to copper-catalyzed azide/alkyne reactions; the strain in the starting alkene lowers the cost of accessing the reaction transition state. To date, cyclobutenes have been looked at very little as substrates for click chemistry.