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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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