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Biotinylated Cell-penetrating Peptides to Study Intracellular Protein-protein Interactions
Published on: December 20, 2017
Drug-Drug Interactions within Protein Cavities Probed by Triplet-Triplet Energy Transfer
Edurne Nuin1, M Consuelo Jiménez1, Germán Sastre1
1†Departamento de Química-Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Camino de Vera s/n, Valencia, Spain.
Abstract:
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.
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