A split β-lactamase sensor for the detection of DNA modification by cisplatin and ruthenium-based chemotherapeutic drugs.

Here we present a split-enzyme sensor approach for the sequence-specific detection of metal-based drug adducts of DNA. Split β-lactamase reporters were constructed using domain A of the High Mobility Group Box 1 protein (HMGB1a) in conjunction with zinc finger DNA-binding domains. As a proof of concept, the sensors were characterized with the well-known drug cisplatin, which forms 1,2-intrastrand crosslinks with DNA that are recognized by HMGB1a.