Highly Stable trans‐Cyclooctene Amino Acids for Live‐Cell Labeling. Issue 35 (15th July 2015)

• Record Type: Journal Article
• Authors: Hoffmann, Jan‐Erik; Plass, Tilman; Nikić, Ivana; Aramburu, Iker Valle; Koehler, Christine; Gillandt, Hartmut; Lemke, Edward A.; Schultz, Carsten
• Is Part Of: Chemistry. Volume 21:Issue 35(2015)
• Page Start: 12266
• Page End: 12270
• Publication Date: 2015-07-15
• Subjects: amino acids -- cell labeling -- organic synthesis -- proteins -- receptors; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201501647
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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. Abstract : Unnatural amino acids : A highly improved synthetic access to axially and equatorially linked trans ‐cyclooct‐2‐ene isomers is described. Furthermore, it was shown 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 (see figure).