European Molecular Biology Laboratory

Embl

Tilman Plass

Carsten Schultz

Edward Lemke

Ivana Nikic

Iker Valle Aramburu

Sigrid Milles

Jan-Erik Hoffmann

Christine Koehler

The present invention relates to compounds of formula: and methods for linking tetrazines with dienophiles to establish at least two linkages by sequentially performing at least two cycloaddition reactions. The methods in particular allow establishing multi-labeling strategies. In particular, the invention relates to methods for forming linkages by cycloaddition reactions, wherein the method comprises reacting a first alkyl-substituted tetrazine with a first dienophile comprising a trans-cyclooctenyl group followed by reacting a second tetrazine with a second dienophile comprising a cyclooctynyl group, wherein the reaction of the first tetrazine with the first dienophile proceeds in the presence of the second dienophile.

Trans-cyclooctene amino and hydroxy acids and their use in multiple cycloaddition reactions for labeling of molecules

The present invention relates to unnatural amino acids comprising a cyclooctynyl or trans-cyclooctenyl analog group and having formula (I) or an acid or base addition salt thereof. The invention also relates to the use of said unnatural amino acids, kits and processes for preparation of polypeptides that comprise one or more than one cyclooctynyl or trans-cyclooctenyl analog group. These polypeptides can be covalently modified by in vitro or in vivo reaction with compounds comprising an azide, nitrile oxide, nitrone, diazocarbonyl or 1,2,4,5-tetrazine group. 

Unnatural amino acids comprising a cyclooctynyl or trans-cyclooctenyl analog group and uses thereof

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Heidelberg, Germany

Tilman Plass