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靶向突变型亨廷顿蛋白的 G-四链体形成适体的截短类似物：更短更好！

Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!

机构信息

Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy.

Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.

出版信息

Int J Mol Sci. 2022 Oct 17;23(20):12412. doi: 10.3390/ijms232012412.

DOI:10.3390/ijms232012412
PMID:36293267
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9604342/
Abstract

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 Huntington's disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.

摘要

我们设计并评估了两个 MS3 适体的类似物，之前的研究表明，它们具有选择性结合和调节突变型亨廷顿蛋白（mHTT）活性的优异能力。原始的 36 -mer MS3 具有形成复杂 G-四链体结构的独特倾向，包括大的多聚体聚集物，已被截断为 33 -mer（命名为 MS3-33）和 17-mer（命名为 MS3-17）。结合使用不同的技术（UV、CD、DSC、凝胶电泳），对这些新型 G-四链体形成适体进行了详细的理化特性分析，在 SH-SY5Y 细胞中进行了体外测试，并在亨廷顿病模型中进行了体内测试，结果表明这些较短的 MS3 衍生寡核苷酸与母体适体相比具有改善的生物活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/f014ad80d86a/ijms-23-12412-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/82ccf38267a4/ijms-23-12412-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/de841bbf545a/ijms-23-12412-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/f014ad80d86a/ijms-23-12412-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/9bf98cdda837/ijms-23-12412-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/2a70ace39f9d/ijms-23-12412-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/2d29415238f9/ijms-23-12412-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/61010d1bd05d/ijms-23-12412-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/82ccf38267a4/ijms-23-12412-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/de841bbf545a/ijms-23-12412-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d195/9604342/f014ad80d86a/ijms-23-12412-g010.jpg

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