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2017-09-13 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Neaga Ioan-Ovidiu, Hambye Stéphanie , Bodoki Ede, Blankert Bertrand , Oprean Radu, "Affinity capillary electrophoresis as fast screening method for oligonucleotides-ligands interaction assessment to identify potentially active compounds in myotonic dystrophy type 1" in EDT Scieces pharmaceutiques : PHD Day, Spa, Belgique, 2017

  • Codes CREF : Chimie analytique (DI1314), Sciences pharmaceutiques (DI3400), Techniques séparatives (DI2729)
  • Unités de recherche UMONS : Analyse pharmaceutique (M130)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)

Abstract(s) :

(Anglais) Myotonic dystrophy type 1, or the Steinert disease, is an autosomal dominant inherited genetic disorder characterized by wasting of the muscles, cataract, cardiac conduction abnormalities and endocrine changes (insulin resistance). At genetic level, the mechanism of the disease is related to a mutation at the DMPK gene characterized by abnormal repeats of the CTG triplet. The transcription of this mutated segment leads to abnormal CUG repeats in the tRNA which in turn can sequestrate an important splicing factor (MBNL-1) leading abnormal protein synthesis to the symptoms of the disease. Several in vitro and in vivo studies showed that different small molecules could disrupt this complex by binding competitively to the CUG region and release the MBNL-1 splicing factor restoring its function. We present an analytical approach that could be complementary to the in vivo techniques and present some advantages compared to the in vitro techniques used (simplicity, low analyte consumption, automation) and could facilitate the fast screening of different ligands. The present work illustrates a capillary electrophoresis (CE) method developed for the study of nucleic acids-ligand using pentamidine as the lead compound. Different compounds, mainly antibiotics, were tested and their interaction with the nucleic acids (both DNA and RNA) were estimated in terms of binding constant and stoichiometry. The data suggest that upon additional optimization this CE method can be employed for the rapid screening of potential ligands, which can further tested by in vitro or cells cultures, thus saving time.