Cracking the triple helix

Triplex DNA structures form when a third strand of DNA binds to the major groove of a DNA double helix. While these structures are important for gene regulation, they can also contribute to genomic instability by interfering with DNA replication and repair, potentially leading to mutations or DNA damage. Investigating these structures in living systems has been challenging because traditional techniques often rely on artificial conditions that fail to replicate the true complexity of cellular environments.

The chemical probe was called photoBQQ to reflect both its chemical structure and function. ‘Photo’ indicates that the probe is activated by light (specifically ultraviolet, UV, light), while ‘BQQ’ stands for benzoquinoquinoxaline, the core chemical structure known for its specificity in binding to triplex DNA. The probe is also comprised of a diazirine moiety that, when exposed to UV light, forms strong bonds with nearby biomolecules, and an alkyne group that allows for further labelling and isolation of the target proteins.

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