Small-Angle scattering applications to the analysis of aptamer structure and conformational changes

14 Jul 2020, 18:30
20m
Zoom 890 9721 5207 ()

Zoom 890 9721 5207

Oral X-ray structural analysis X-ray structural analysis

Speaker

Roman Moryachkov (Kirensky Institute of Physics)

Description

At present different agents are developing for diagnostics and treatment of cancer - one of the main reasons of human deaths. Especially perspective examples are aptamers - single-stranded DNA or RNA molecules which are compact analogs of the antibodies with low immune response, have a short length (10-100 nucleotides), well-defined spatial structure and surface charge distribution providing highly specific binding with their targets - proteins in the tumor cells. It allows one to use aptamers as the agents for the visualisation the cancer cells and tissues in organism and also as the carriers for active molecules, labels, nanoparticles, toxic entities to deseased tissue cells. To define the function and parameters of the activity for the aptamers and to localize the specific binding epitopes on the surface of both aptamers and the target proteins, it is necessary to know the spatial structure of these molecules.
For this purpose the Small-Angle X-ray Scattering (SAXS) method was used, which is applied in a high quality at the synchrotron radiation sources due to the high intensity of the emitted X-rays, ability to change the wavelength and beam size for the experiment. SAXS method is used to carry out the measurements on the biomolecules in solution, without crystallisation which is mostly impossible for single-stranded nucleic acids. One can create a native environment for the molecules under study, or inversely to track the conformational changes during varying temperature, pH and other parameters.
Here we present the results of revealing and adjusting the 3D spatial structures of the DNA molecules using the SAXS method in solution and the molecular simulation method based on the experimental SAXS data. This combination yields an information about the molecule structure, possible conformational changes, parameters of the aptamer-protein complexation, that in a perspective will be useful to optimize the development procedure of the theranostics agents against the socially important deseases.

This work is partially supported by RFBR grant №18-32-00478.

Primary authors

Roman Moryachkov (Kirensky Institute of Physics) Vladimir Zabluda (Kirensky Institute of Physics Russian Academy of Sciences, Siberian Branch) Mrs Vera Spiridonova (A.N. Belozersky Institute Of Physico-Chemical Biology, Lomonosov Moscow State University) Ms Polina Artyushenko (Federal Research Center “Krasnoyarsk Science Center” Siberian Branch of the Russian Academy of Sciences) Ms Irina Shchugoreva (Federal Research Center “Krasnoyarsk Science Center” Siberian Branch of the Russian Academy of Sciences) Mrs Anna Berlina (A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences) Mr Georgy Peters (NRC Kurchatov Institute) Mrs Anna Kichkailo (Federal Research Center “Krasnoyarsk Science Center” Siberian Branch of the Russian Academy of Sciences) Mr Alexey Sokolov (Kirensky Institute of Physics)

Presentation Materials