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Drug–Drug Interactions within Protein Cavities Probed by Triplet–Triplet Energy Transfer

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journal contribution
posted on 16.12.2015, 22:50 by Edurne Nuin, M. Consuelo Jiménez, Germán Sastre, Inmaculada Andreu, Miguel A. Miranda
A new direct and noninvasive methodology based on transient absorption spectroscopy has been developed to probe the feasibility of drug–drug interactions within a common protein binding site. The simultaneous presence of (R)-cinacalcet (CIN) and (S)-propranolol (PPN) within human or bovine α1-acid glycoproteins (AAGs) is revealed by detection of 3CIN* as the only transient species after laser flash photolysis of CIN/PPN/AAG mixtures at 308 nm. This is the result of triplet–triplet energy transfer from 3PPN* to CIN, which requires close contact between the two drugs within the same biological compartment. Similar results are obtained with nabumetone and CIN as donor/acceptor partners. This new methodology can, in principle, be extended to a variety of drug/drug/biomolecule combinations.