Influence of oligoribonucleotides on the conformation and stability of interferon

  • R. O. Nikolaiev Institute of Molecular Biology and Genetics of Natl. Acad. Sci. of Ukraine, Ukraine, 03143, Kyiv, Akad. Zabolotnogo str., 150
  • M. M. Vivcharyk Institute of Molecular Biology and Genetics of Natl. Acad. Sci. of Ukraine, Ukraine, 03143, Kyiv, Akad. Zabolotnogo str., 150
  • S. I. Chernykh Institute of Molecular Biology and Genetics of Natl. Acad. Sci. of Ukraine, Ukraine, 03143, Kyiv, Akad. Zabolotnogo str., 150
  • Z. Yu. Tkachuk Institute of Molecular Biology and Genetics of Natl. Acad. Sci. of Ukraine, Ukraine, 03143, Kyiv, Akad. Zabolotnogo str., 150
DOI: https://doi.org/10.7124/visnyk.utgis.17.2.1217

Abstract

Aim. To study the ability of yeast RNA oligoribonucleotides (ORNs) and their complexes withD-mannitol to influence the conformation and thermal stability of interferon (INF) α-2b. Methods. The ability of oligoribonucleotide drugs to bind to INF α-2b was studied using its fluorescence quenching method. The effect of ORN drugs on protein stability was studied by analyzing the thermal stability of INF. To confirm their influence on the conformation of the INF, we investigated the spectra of circular dichroism. Results. The ORN complexes with D-mannitol, due to their better protein binding, have been shown to have a much higher effect on the conformation and thermal stability of interferon α-2b than ORN. ORNs and their complexes with D-mannitol also increase the thermal stabilization of interferon. The addition of ORN and ORN with D-mannitol to INF leads to a decrease in the content of α-helical components in the protein structure and an increase in β-components and unstructured parts of the protein molecule. Addition of the ORN complex: D-mannitol, unlike the ORN, changes the architecture of the tertiary INF structure. Conclusions. Therefore, the ORN complexes with D-mannitol have a much higher effect on the conformation and thermal stability of interferon α-2b than the parent drug ORN. The more specific binding of oligonucleotides can probably explain this in the presence of mannitol to the protein. ORNs and ORN complexes with D-mannitol also increase the thermal stabilization of interferon by 2 and 1.8 °C, respectively. The addition of ORNs and ORN complexes with D-mannitol leads to a decrease in the content of α- helical components in the protein structure and an increase in antiparallel β-sheets, β-turns, and unstructured elements. In the presence of mannitol in the ORN molecule, the structure of INF changes more intensively. Addition of ORN complexes: D-mannitol to INF, unlike ORN, changes the architecture of the tertiary protein structure from a 2-layer sandwich to an alpha-beta complex.
Keywords: oligonucleotides; interferon; mannitol; secondary protein structure.

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