Structural and Functional Aspects of G-Quadruplex Aptamers Which Bind a Broad Range of Influenza A Viruses
An aptamer is a synthetic oligonucleotide with a unique spatial structure that provides specific binding to a target. To date, several aptamers to hemagglutinin of the influenza A virus have been described, which vary in affinity and strain specificity. Among them, the DNA aptamer RHA0385 is able to...
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MDPI AG
2020-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/1/119 |
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| author | Anastasia A. Novoseltseva Nikita M. Ivanov Roman A. Novikov Yaroslav V. Tkachev Dmitry A. Bunin Alexandra S. Gambaryan Vadim N. Tashlitsky Alexander M. Arutyunyan Alexey M. Kopylov Elena G. Zavyalova |
| author_facet | Anastasia A. Novoseltseva Nikita M. Ivanov Roman A. Novikov Yaroslav V. Tkachev Dmitry A. Bunin Alexandra S. Gambaryan Vadim N. Tashlitsky Alexander M. Arutyunyan Alexey M. Kopylov Elena G. Zavyalova |
| author_sort | Anastasia A. Novoseltseva |
| collection | DOAJ |
| description | An aptamer is a synthetic oligonucleotide with a unique spatial structure that provides specific binding to a target. To date, several aptamers to hemagglutinin of the influenza A virus have been described, which vary in affinity and strain specificity. Among them, the DNA aptamer RHA0385 is able to recognize influenza hemagglutinins with highly variable sequences. In this paper, the structure of RHA0385 was studied by circular dichroism spectroscopy, nuclear magnetic resonance, and size-exclusion chromatography, demonstrating the formation of a parallel G-quadruplex structure. Three derivatives of RHA0385 were designed in order to determine the contribution of the major loop to affinity. Shortening of the major loop from seven to three nucleotides led to stabilization of the scaffold. The affinities of the derivatives were studied by surface plasmon resonance and an enzyme-linked aptamer assay on recombinant hemagglutinins and viral particles, respectively. The alterations in the loop affected the binding to influenza hemagglutinin, but did not abolish it. Contrary to aptamer RHA0385, two of the designed aptamers were shown to be conformationally homogeneous, retaining high affinities and broad binding abilities for both recombinant hemagglutinins and whole influenza A viruses. |
| first_indexed | 2024-12-12T04:03:23Z |
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| id | doaj.art-c9d96ed7d4234823841d448623e2e725 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-12T04:03:23Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-c9d96ed7d4234823841d448623e2e7252022-12-22T00:38:51ZengMDPI AGBiomolecules2218-273X2020-01-0110111910.3390/biom10010119biom10010119Structural and Functional Aspects of G-Quadruplex Aptamers Which Bind a Broad Range of Influenza A VirusesAnastasia A. Novoseltseva0Nikita M. Ivanov1Roman A. Novikov2Yaroslav V. Tkachev3Dmitry A. Bunin4Alexandra S. Gambaryan5Vadim N. Tashlitsky6Alexander M. Arutyunyan7Alexey M. Kopylov8Elena G. Zavyalova9Chemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaChemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaEngelhardt Institute of Molecular Biology RAS, 119991 Moscow, RussiaEngelhardt Institute of Molecular Biology RAS, 119991 Moscow, RussiaChemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaChumakov Federal Scientific Centre for Research and Development of Immune and Biological Products RAS, 108819 Moscow, RussiaChemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaBelozersky Research Institute of Physical Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaChemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaChemistry Department, Lomonosov Moscow State University, 119991 Moscow, RussiaAn aptamer is a synthetic oligonucleotide with a unique spatial structure that provides specific binding to a target. To date, several aptamers to hemagglutinin of the influenza A virus have been described, which vary in affinity and strain specificity. Among them, the DNA aptamer RHA0385 is able to recognize influenza hemagglutinins with highly variable sequences. In this paper, the structure of RHA0385 was studied by circular dichroism spectroscopy, nuclear magnetic resonance, and size-exclusion chromatography, demonstrating the formation of a parallel G-quadruplex structure. Three derivatives of RHA0385 were designed in order to determine the contribution of the major loop to affinity. Shortening of the major loop from seven to three nucleotides led to stabilization of the scaffold. The affinities of the derivatives were studied by surface plasmon resonance and an enzyme-linked aptamer assay on recombinant hemagglutinins and viral particles, respectively. The alterations in the loop affected the binding to influenza hemagglutinin, but did not abolish it. Contrary to aptamer RHA0385, two of the designed aptamers were shown to be conformationally homogeneous, retaining high affinities and broad binding abilities for both recombinant hemagglutinins and whole influenza A viruses.https://www.mdpi.com/2218-273X/10/1/119dna aptamerg-quadruplexinfluenza virushemagglutininaffinitystructure–activity relationship |
| spellingShingle | Anastasia A. Novoseltseva Nikita M. Ivanov Roman A. Novikov Yaroslav V. Tkachev Dmitry A. Bunin Alexandra S. Gambaryan Vadim N. Tashlitsky Alexander M. Arutyunyan Alexey M. Kopylov Elena G. Zavyalova Structural and Functional Aspects of G-Quadruplex Aptamers Which Bind a Broad Range of Influenza A Viruses Biomolecules dna aptamer g-quadruplex influenza virus hemagglutinin affinity structure–activity relationship |
| title | Structural and Functional Aspects of G-Quadruplex Aptamers Which Bind a Broad Range of Influenza A Viruses |
| title_full | Structural and Functional Aspects of G-Quadruplex Aptamers Which Bind a Broad Range of Influenza A Viruses |
| title_fullStr | Structural and Functional Aspects of G-Quadruplex Aptamers Which Bind a Broad Range of Influenza A Viruses |
| title_full_unstemmed | Structural and Functional Aspects of G-Quadruplex Aptamers Which Bind a Broad Range of Influenza A Viruses |
| title_short | Structural and Functional Aspects of G-Quadruplex Aptamers Which Bind a Broad Range of Influenza A Viruses |
| title_sort | structural and functional aspects of g quadruplex aptamers which bind a broad range of influenza a viruses |
| topic | dna aptamer g-quadruplex influenza virus hemagglutinin affinity structure–activity relationship |
| url | https://www.mdpi.com/2218-273X/10/1/119 |
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