Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!
Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to fo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12412 |
| _version_ | 1797407120500457472 |
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| author | Claudia Riccardi Federica D’Aria Dominga Fasano Filomena Anna Digilio Maria Rosaria Carillo Jussara Amato Laura De Rosa Simona Paladino Mariarosa Anna Beatrice Melone Daniela Montesarchio Concetta Giancola |
| author_facet | Claudia Riccardi Federica D’Aria Dominga Fasano Filomena Anna Digilio Maria Rosaria Carillo Jussara Amato Laura De Rosa Simona Paladino Mariarosa Anna Beatrice Melone Daniela Montesarchio Concetta Giancola |
| author_sort | Claudia Riccardi |
| collection | DOAJ |
| description | Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a <i>Drosophila</i> Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer. |
| first_indexed | 2024-03-09T03:36:41Z |
| format | Article |
| id | doaj.art-9ee2118330bc416e9eb9c2c184cb036c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:36:41Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9ee2118330bc416e9eb9c2c184cb036c2023-12-03T14:47:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201241210.3390/ijms232012412Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!Claudia Riccardi0Federica D’Aria1Dominga Fasano2Filomena Anna Digilio3Maria Rosaria Carillo4Jussara Amato5Laura De Rosa6Simona Paladino7Mariarosa Anna Beatrice Melone8Daniela Montesarchio9Concetta Giancola10Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania Luigi Vanvitelli, 80131 Naples, ItalyResearch Institute on Terrestrial Ecosystems (IRET), UOS Naples-CNR, 80131 Naples, ItalyDepartment of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania Luigi Vanvitelli, 80131 Naples, ItalyDepartment of Chemical Sciences, University of Naples Federico II, 80126 Naples, ItalyDepartment of Pharmacy, University of Naples Federico II, 80131 Naples, ItalyTwo analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a <i>Drosophila</i> Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.https://www.mdpi.com/1422-0067/23/20/12412G-quadruplexaptamersphysicochemical characterizationHuntington’s disease<i>Drosophila melanogaster</i> model |
| spellingShingle | Claudia Riccardi Federica D’Aria Dominga Fasano Filomena Anna Digilio Maria Rosaria Carillo Jussara Amato Laura De Rosa Simona Paladino Mariarosa Anna Beatrice Melone Daniela Montesarchio Concetta Giancola Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better! International Journal of Molecular Sciences G-quadruplex aptamers physicochemical characterization Huntington’s disease <i>Drosophila melanogaster</i> model |
| title | Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better! |
| title_full | Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better! |
| title_fullStr | Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better! |
| title_full_unstemmed | Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better! |
| title_short | Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better! |
| title_sort | truncated analogues of a g quadruplex forming aptamer targeting mutant huntingtin shorter is better |
| topic | G-quadruplex aptamers physicochemical characterization Huntington’s disease <i>Drosophila melanogaster</i> model |
| url | https://www.mdpi.com/1422-0067/23/20/12412 |
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