Excited-State Proton Transfer Can Tune the Color of Protein Fluorescent Markers

Daiana T. Mancini (1) , Kakali Sen (2) , Mario Barbatti (3) , Walter Thiel (4) , Teodorico C. Ramalho (1)

1 UFLA - Universidade Federal de Lavras = Federal University of Lavras
2 UPMC - Université Pierre et Marie Curie - Paris 6
3 ICR - Institut de Chimie Radicalaire
4 Max-Planck-Institut für Kohlenforschung (Coal Research)

We show by quantum mechanical/molecular mechanical (QM/MM) simulations that phenylbenzothiazoles undergoing an excited-state proton transfer (ESPT) can be used to probe protein binding sites. For 2-(2'-hydroxy-4'-aminophenyl)benzothiazole (HABT) bound to a tyrosine kinase, the absolute and relative intensities of the fluorescence bands arising from the enol and keto forms are found to be strongly dependent on the active-site conformation. The emission properties are tuned by hydrogen-bonding interactions of HABT with the neighboring amino acid T766 and with active-site water. The use of ESPT tuners opens the possibility of creating two-color fluorescent markers for protein binding sites, with potential applications in the detection of mutations in cancer cell lines.

Domaines: Chimie théorique et/ou physique

Daiana T. Mancini, Kakali Sen, Mario Barbatti, Walter Thiel, Teodorico C. Ramalho. Excited-State Proton Transfer Can Tune the Color of Protein Fluorescent Markers. ChemPhysChem, 2015, 16 (16), pp.3444--3449. ⟨10.1002/cphc.201500744⟩. ⟨hal-01415155⟩