A Minimal, Unstrained S-Allyl Handle for Pre-Targeting Diels-Alder Bioorthogonal Labeling in Live Cells

Angew Chem Int Ed Engl. 2016 Nov 14;55(47):14683-14687. doi: 10.1002/anie.201608438. Epub 2016 Oct 20.

Abstract

The unstrained S-allyl cysteine amino acid was site-specifically installed on apoptosis protein biomarkers and was further used as a chemical handle and ligation partner for 1,2,4,5-tetrazines by means of an inverse-electron-demand Diels-Alder reaction. We demonstrate the utility of this minimal handle for the efficient labeling of apoptotic cells using a fluorogenic tetrazine dye in a pre-targeting approach. The small size, easy chemical installation, and selective reactivity of the S-allyl handle towards tetrazines should be readily extendable to other proteins and biomolecules, which could facilitate their labeling within live cells.

Keywords: Diels-Alder reactions; apoptosis; bioorthogonal labeling; pre-targeting; unstrained alkenes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cycloaddition Reaction
  • HEK293 Cells
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Tetrazoles / chemical synthesis*
  • Tetrazoles / chemistry

Substances

  • Tetrazoles