A1 Journal article (refereed)
The Role of Small-Angle X-Ray Scattering and Molecular Simulations in 3D Structure Elucidation of a DNA Aptamer Against Lung Cancer (2021)

Morozov, D., Mironov, V., Moryachkov, R. V., Shchugoreva, I. A., Artyushenko, P. V., Zamay, G. S., Kolovskaya, O. S., Zamay, T. N., Krat, A. V., Molodenskiy, D. S., Zabluda, V. N., Veprintsev, D. V., Sokolov, A. E., Zukov, R. A., Berezovski, M. V., Tomilin, F. N., Fedorov, D. G., Alexeev, Y., & Kichkailo, A. S. (2021). The Role of Small-Angle X-Ray Scattering and Molecular Simulations in 3D Structure Elucidation of a DNA Aptamer Against Lung Cancer. Molecular Therapy Nucleic Acids, 25, 316-327. https://doi.org/10.1016/j.omtn.2021.07.015

JYU authors or editors

Morozov, Dmitry

Publication details

All authors or editors: Morozov, Dmitry; Mironov, Vladimir; Moryachkov, Roman V.; Shchugoreva, Irina A.; Artyushenko, Polina V.; Zamay, Galina S.; Kolovskaya, Olga S.; Zamay, Tatiana N.; Krat, Alexey V.; Molodenskiy, Dmitry S.; et al.

Journal or series: Molecular Therapy Nucleic Acids

eISSN: 2162-2531

Publication year: 2021

Volume: 25

Pages range: 316-327

Publisher: Elsevier

Publication country: United States

Publication language: English

DOI: https://doi.org/10.1016/j.omtn.2021.07.015

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/77458

Abstract

Aptamers are short, single-stranded DNA or RNA oligonucleotide molecules that function as synthetic analogs of antibodies and bind to a target molecule with high specificity. Aptamer affinity entirely depends on its tertiary structure and charge distribution. Therefore, length and structure optimization are essential for increasing aptamer specificity and affinity. Here we present a general optimization procedure for finding most populated atomistic structures of DNA aptamers. Based on the existed aptamer LC-18 for lung adenocarcinoma, a new truncated aptamer LC-18t was developed. A three-dimensional shape of LC-18t was reported based on small-angle X-ray scattering (SAXS) experiments and molecular modeling by fragment molecular orbital or molecular dynamic methods. Molecular simulations revealed an ensemble of possible aptamer conformations in solution that were in close agreement with measured SAXS data. The truncated aptamer LC-18t had stronger binding to cancerous cells in lung tumor tissues and shared the binding site with the original larger aptamer. The suggested approach reveals 3D shapes of aptamers and helps in designing better affinity probes.

Keywords: nucleotides; oligonucleotides; antibodies; immune response; cancer cells; molecular dynamics; simulation