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Duplex/quadruplex oligonucleotides: Role of the duplex domain in the stabilization of a new generation of highly effective anti-thrombin aptamers.

Authors
  • Russo Krauss, Irene1
  • Napolitano, Valeria2
  • Petraccone, Luigi2
  • Troisi, Romualdo2
  • Spiridonova, Vera3
  • Mattia, Carlo Andrea4
  • Sica, Filomena5
  • 1 Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Naples, Italy; CSGI - Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase, Via della Lastruccia 3, I-50019, Sesto Fiorentino, FI, Italy. , (Italy)
  • 2 Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Naples, Italy. , (Italy)
  • 3 A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia.
  • 4 Department of Pharmacy, University of Salerno, Via Ponte Don Melillo, I-84084, Fisciano, SA, Italy. , (Italy)
  • 5 Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Naples, Italy. Electronic address: [email protected] , (Italy)
Type
Published Article
Journal
International journal of biological macromolecules
Publication Date
Oct 10, 2017
Identifiers
DOI: 10.1016/j.ijbiomac.2017.10.033
PMID: 29024684
Source
Medline
Keywords
License
Unknown

Abstract

Recently, mixed duplex/quadruplex oligonucleotides have attracted great interest for use as biomedical aptamers. In the case of anti-thrombin aptamers, the addition of duplex-forming sequences to a G-quadruplex module identical or very similar to the best-known G-quadruplex of the Thrombin Binding Aptamer (HD1) results in new or improved biological properties, such as higher activity or different recognition properties with respect to HD1. Remarkably, this bimodular fold was hypothesized, based on its sequence, for the only anti-thrombin aptamer in advanced clinical trial, NU172. Whereas cation modulation of G-quadruplex conformation and stability is well characterized, only few data from similar analysis on duplex/quadruplex oligonucleotides exist. Here we have performed a characterization of structure and stability of four different duplex/quadruplex anti-thrombin aptamers, including NU172, in the presence of different cations and in physiological-mimicking conditions in comparison to HD1, by means of spectroscopic techniques (UV and circular dichroism) and differential scanning calorimetry. Our data show a strong reciprocal influence of each domain on the stability of the other and in particular suggest a stabilizing effect of the duplex region in the presence of solutions mimicking the physiological conditions, strengthening the idea that bimodular aptamers present better therapeutic potentialities than those containing a single G-quadruplex domain.

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