Complexes and Supramolecular Associates of Dodecyl-Containing Oligonucleotides with Serum Albumin

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Anna S. Pavlova^1,a*, Valeriya V. Ilyushchenko¹, Maxim S. Kupryushkin¹, Timofey D. Zharkov¹, Evgeniya S. Dyudeeva¹, Irina A. Bauer¹, Alexey S. Chubarov¹, Dmitrii V. Pyshnyi¹, and Inna A. Pyshnaya^1,b*

¹Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

^* To whom correspondence should be addressed.

Received April 26, 2023; Revised June 26, 2023; Accepted July 4, 2023

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Serum albumin is currently in the focus of biomedical research as a promising platform for the creation of multicomponent self-assembling systems due to the presence of several sites with high binding affinity of various compounds in its molecule, including lipophilic oligonucleotide conjugates. In this work, we investigated the stoichiometry of the dodecyl-containing oligonucleotides binding to bovine and human serum albumins using an electrophoretic mobility shift assay. The results indicate the formation of the albumin-oligonucleotide complexes with a stoichiometry of about 1 : (1.25 ± 0.25) under physiological-like conditions. Using atomic force microscopy, it was found that the interaction of human serum albumin with the duplex of complementary dodecyl-containing oligonucleotides resulted in the formation of circular associates with a diameter of 165.5 ± 94.3 nm and 28.9 ± 16.9 nm in height, and interaction with polydeoxyadenylic acid and dodecyl-containing oligothymidylate resulted in formation of supramolecular associates with the size of about 315.4 ± 70.9 and 188.3 ± 43.7 nm, respectively. The obtained data allow considering the dodecyl-containing oligonucleotides and albumin as potential components of the designed self-assembling systems for solving problems of molecular biology, biomedicine, and development of unique theranostics with targeted action.

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KEY WORDS: serum albumin, dodecyl-containing oligonucleotides, protein–nucleic acids complexes, biopolymers self-assembly, supramolecular associates, nucleic acids delivery

DOI: 10.1134/S0006297923080102

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