title: Highly Stable trans-Cyclooctene Amino Acids for Live-Cell Labeling.
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.
authors.affiliation: Cell Biology & Biophysics Unit, Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstr.1, 69117 Heidelberg (Germany), Fax: (+49) 6221-387-518.
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Hoffmann
authors.affiliation: Cell Biology & Biophysics Unit, Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstr.1, 69117 Heidelberg (Germany), Fax: (+49) 6221-387-518.
authors.forename: Tilman
authors.initials: T
authors.lastname: Plass
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstr.1, 69117 Heidelberg (Germany).
authors.forename: Ivana
authors.initials: I
authors.lastname: Nikić
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstr.1, 69117 Heidelberg (Germany).
authors.forename: Iker Valle
authors.initials: IV
authors.lastname: Aramburu
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstr.1, 69117 Heidelberg (Germany).
authors.forename: Christine
authors.initials: C
authors.lastname: Koehler
authors.affiliation: SiChem GmbH, Fahrenheitstr. 1, 28359 Bremen (Germany).
authors.forename: Hartmut
authors.initials: H
authors.lastname: Gillandt
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstr.1, 69117 Heidelberg (Germany).
authors.forename: Edward A
authors.initials: EA
authors.lastname: Lemke
authors.affiliation: Cell Biology & Biophysics Unit, Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstr.1, 69117 Heidelberg (Germany), Fax: (+49) 6221-387-518. schultz@embl.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schultz
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D002460:Cell Line; D034242:Cyclooctanes / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D000596:Amino Acids; D034242:Cyclooctanes
keywords: amino acids; cell labeling; organic synthesis; proteins; receptors