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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604342/ https://www.ncbi.nlm.nih.gov/pubmed/36293267 http://dx.doi.org/10.3390/ijms232012412 |
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author | Riccardi, Claudia D’Aria, Federica Fasano, Dominga Digilio, Filomena Anna Carillo, Maria Rosaria Amato, Jussara De Rosa, Laura Paladino, Simona Melone, Mariarosa Anna Beatrice Montesarchio, Daniela Giancola, Concetta |
author_facet | Riccardi, Claudia D’Aria, Federica Fasano, Dominga Digilio, Filomena Anna Carillo, Maria Rosaria Amato, Jussara De Rosa, Laura Paladino, Simona Melone, Mariarosa Anna Beatrice Montesarchio, Daniela Giancola, Concetta |
author_sort | Riccardi, Claudia |
collection | PubMed |
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 Drosophila Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer. |
format | Online Article Text |
id | pubmed-9604342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96043422022-10-27 Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better! Riccardi, Claudia D’Aria, Federica Fasano, Dominga Digilio, Filomena Anna Carillo, Maria Rosaria Amato, Jussara De Rosa, Laura Paladino, Simona Melone, Mariarosa Anna Beatrice Montesarchio, Daniela Giancola, Concetta Int J Mol Sci Article 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 Drosophila Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer. MDPI 2022-10-17 /pmc/articles/PMC9604342/ /pubmed/36293267 http://dx.doi.org/10.3390/ijms232012412 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Riccardi, Claudia D’Aria, Federica Fasano, Dominga Digilio, Filomena Anna Carillo, Maria Rosaria Amato, Jussara De Rosa, Laura Paladino, Simona Melone, Mariarosa Anna Beatrice Montesarchio, Daniela Giancola, Concetta Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better! |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604342/ https://www.ncbi.nlm.nih.gov/pubmed/36293267 http://dx.doi.org/10.3390/ijms232012412 |
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