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Analytical and Bioanalytical Chemistry

, Volume 410, Issue 18, pp 4495–4507 | Cite as

Affinity capillary electrophoresis for identification of active drug candidates in myotonic dystrophy type 1

  • Ioan O. Neaga
  • Stephanie Hambye
  • Ede Bodoki
  • Claudio Palmieri
  • Eugénie Ansseau
  • Alexandra Belayew
  • Radu Oprean
  • Bertrand BlankertEmail author
Research Paper

Abstract

Myotonic dystrophy type 1 (DM1) is an autosomal dominantly inherited degenerative disease with a slow progression. At the present, there is no commercially available treatment, but sustained effort is currently undertaken for the development of a promising lead compound. In the present paper we report the development of a fast, versatile, and cost-effective affinity capillary electrophoresis (ACE) method for the screening and identification of potential drug candidates targeting pathological ARN probes relevant for DM1. The affinity studies were conducted in physiologically relevant conditions using 50 mM HEPES buffer (pH 7.4) in a fused silica capillary dynamically coated with poly(ethylene oxide), by testing a library of potential ligands against (CUG)50 RNA as target probe with a total run time of 4–5 h/ligand. For the most promising ligands, their affinity parameters were assessed and some results formerly reported on the affinity of pentamidine (PTMD) and neomycin against CUG repeats were confirmed. To the best of the authors’ knowledge, the estimated binding stoichiometry for some of the tested compounds (i.e., ~ 121:1 for PTMD against the tested RNA probe) is reported for the first time. Additionally, the potential of a novel pentamidine like compound, namely 1,2-ethane bis-1-amino-4-benzamidine (EBAB) with much lower in vivo toxicity than its parent compound has also been confirmed studying its effect on a live cell model by fluorescence microscopy. Further tests, such as the evaluation of the rescue in the mis-splicing of the involved genes, can be performed to corroborate the potential therapeutic value of EBAB in DM1 treatment.

Graphical abstract

Keywords

Myotonic dystrophy type 1 Ligand screening Affinity capillary electrophoresis Fluorescence in situ hybridization Pentamidine 

Notes

Funding information

The authors are grateful for financial support from the ABMM (Belgium) and “Iuliu Hațieganu” University of Medicine and Pharmacy (Cluj-Napoca, Romania) through the doctoral research project PCD #7690/78/15.04.2016. Ioan Neaga had a co-financing from the University of Mons.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ioan O. Neaga
    • 1
    • 2
  • Stephanie Hambye
    • 1
  • Ede Bodoki
    • 2
  • Claudio Palmieri
    • 1
  • Eugénie Ansseau
    • 3
  • Alexandra Belayew
    • 3
  • Radu Oprean
    • 2
  • Bertrand Blankert
    • 1
    Email author
  1. 1.Laboratory of Pharmaceutical Analysis, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and TechnologyUniversity of MonsMonsBelgium
  2. 2.Analytical Chemistry Department“Iuliu Hațieganu” University of Medicine and PharmacyCluj-NapocaRomania
  3. 3.Laboratory of Molecular Biology, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and TechnologyUniversity of MonsMonsBelgium

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