RESUMEN
Two Keggin polyoxometalates were used as new copper ligands to counteract the effects of CuII(Amyloid-ß) interaction. Their ability to remove CuII from CuII(Amyloid-ß), to stop CuII(Amyloid-ß) induced formation of reactive oxygen species and to restore apo-like self-assembly of CuII(Amyloid-ß) was shown.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/antagonistas & inhibidores , Aniones/farmacología , Quelantes/farmacología , Cobre/farmacología , Polielectrolitos/farmacología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Aniones/química , Quelantes/síntesis química , Quelantes/química , Cobre/química , Humanos , Polielectrolitos/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Bioorthogonal fluorescent turn-on reactions are attractive for the sensitive real-time detection of a variety of phenomena including bioconjugation, chemical reactivity, and material assembly. Herein we describe the use of 3,4-disubstituted sydnones, a singular class of mesoionic dipoles, for highly fluorescent turn-on copper-free click cycloadditions with the fluorogenic dibenzocyclooctyne Fl-DIBO. Coherent with time-dependent density functional theory calculations, the pyrazole cycloadducts were found to be highly fluorescent with compelling photophysical properties including excellent fluorescence enhancement (up to 240-fold), high quantum yields (over 45%), and large Stokes shift (over 100 nm). Furthermore, the good stability and reactivity of 4-chlorosydnones with Fl-DIBO allowed us to employ them as chemical reporters for the challenging detection of modified-proteins in complex cellular extracts, with exquisite specificity in no-wash conditions. This novel fluorogenic system significantly expands our chemical biology toolbox and should be beneficial in countless applications.
