In recent years, increasing attention has been focused on the development of techniques directed toward studying interactions between biomolecules in living systems. Advances in biomolecular labeling and photocrosslinking technologies have provided powerful tools to study such interactions, even when they are weak and/or short-lived. However, this area still faces significant challenges, including the incorporation of photocrosslinking tags into specific biomolecules and the detection/purification of crosslinked complexes. Here, a bicyclo[6.1.0]nonyne (BCN)-based cyclooctyne reagent bearing a photocrosslinking diazirine (DAz) group and a biotin affinity handle, named BCN-DAz-Biotin, is reported. This trifunctional probe capitalizes on bioorthogonal chemistry and is the first reagent capable of simultaneously delivering photocrosslinking and affinity functionalities to azide-labeled biomolecules in living cells. Photocrosslinking and affinity functionalities allow for the photoactivated covalent capture and enrichment/detection of interacting species, respectively. Thus, for biomolecules that can be azide-labeled for bioorthogonal chemistry applications, BCN-DAz-Biotin can facilitate the study of their interactions in native settings.

Trifunctional cyclooctyne for modifying azide-labeled biomolecules with photocrosslinking and affinity tags

251st National Meeting (2016)

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