Drug-Drug Interactions within Protein Cavities Probed by Triplet-Triplet Energy Transfer.
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 (3)CIN* 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 (3)PPN* 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.
†Departamento de Química-Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Camino de Vera s/n, Valencia, Spain.
Edurne
E
Nuin
†Departamento de Química-Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Camino de Vera s/n, Valencia, Spain.
M Consuelo
MC
Jiménez
†Departamento de Química-Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Camino de Vera s/n, Valencia, Spain.
Germán
G
Sastre
‡Unidad mixta de investigación IIS La Fe-UPV, Hospital La Fe, Avda. Campanar 21, 46009 Valencia, Spain.
Inmaculada
I
Andreu
†Departamento de Química-Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Camino de Vera s/n, Valencia, Spain.
Miguel A
MA
Miranda
cinacalcet; laser flash photolysis; nabumetone; propranolol; triplet excited state; α1-acid glycoprotein