January 1, 2015

Highly Stable trans-Cyclooctene Amino Acids for Live-Cell Labeling.

Jan-Erik Hoffmann, Tilman Plass, Ivana Nikić, Iker Valle Aramburu, Christine Koehler, Hartmut Gillandt, Edward A Lemke, Carsten Schultz
(*) equal first  authors

trans-Cyclooctene groups incorporated into proteins via non-canonical amino acids (ncAAs) are emerging as specific handles for bioorthogonal chemistry. Here, we present a highly improved synthetic access to the axially and the equatorially linked trans-cyclooct-2-ene isomers (1 a,b). We further show that the axially connected isomer has a half-life about 10 times higher than the equatorial isomer and reacts with tetrazines much faster, as determined by stopped-flow experiments. The improved properties resulted in different labeling performance of the insulin receptor on the surface of intact cells.

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