Conformational changes of secondary and tertiary structures of interferon α–2b under the influence of oligoribonucleotidesbased drugs

Abstract

At this stage of our investigation, we studied the ability of oligoribonucleotides from total yeast RNA (ORNs) and oligoribonucleotides-Dmannitol complexes to affect the conformation and stability of interferon (IFN) α-2b – a key protein of the antiviral cell defense mechanism. Obtained thermal denaturation profiles of IFN α–2b alone and in the presence of ORNs and ORNs-D-mannitol complexes show that the addition of these ligands led to an increase of thermal stabilization of protein of 2 and 1.8 0C respectively. The dissociation constant between INF and total yeast ORNs was Kd =2.88±1.14µM and between INF and ORNs with D-mannitol – Kd =0,92±0.23µM. The analysis of IFN secondary structure changes by Bestsel shows that addition of ORNs and ORNs-D-mannitol complexes led to a decrease of α-helix components in the protein structure and to an increase of antiparallel β-stand, β-turn, and random coil components. At the same time, the analysis of the tertiary structure shows that adding ORNs-D-mannitol changes the architecture of the protein from the 2-layer sandwich to alpha-beta complex. On the other hand, adding ORNs did not cause any change in the tertiary structure.