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新型含脂环侧链双子表面活性剂对溶液中 DNA 结构相的影响。

The influence of novel gemini surfactants containing cycloalkyl side-chains on the structural phases of DNA in solution.

机构信息

Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland.

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.

出版信息

Colloids Surf B Biointerfaces. 2015 Jul 1;131:83-92. doi: 10.1016/j.colsurfb.2015.04.042. Epub 2015 Apr 27.

Abstract

Very important to gene therapy is the delivery system of the nucleic acids (called a vector), which will enhance the efficiency of the transport of new DNA into cells whilst protecting against damage. A promising alternative to the currently used viral vectors are the systems based on amphiphilic compounds - lipoplexes. Among them, gemini surfactants, which consist of two hydrophobic chains and two cationic heads connected by a linker - spacer group, appear to be promising candidates. The subject of this study involves two gemini surfactants, alkoxy derivatives of bis-imidazolium quaternary salts, differing in the length of their spacer groups and how they interact with two types of salmon sperm DNA (low and high molecular weight (MW)) or plasmid DNA (pDNA). The mixtures of gemini surfactants with nucleic acids of differing p/n ratios (positive-to-negative charge ratio) were characterised by small angle X-ray scattering (SAXS) of synchrotron radiation, dynamic light scattering (DLS), circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM) and gel electrophoresis techniques. This analysis allows for the selection of the most suitable and promising candidates for non-viral vectors in gene therapy, determination of the conditions needed to form stable complexes, identification of conformational changes in the DNA molecules upon interactions with gemini surfactants and in some cases, determination of the structures formed in these lipoplexes.

摘要

非常重要的是基因治疗的传递系统的核酸(称为载体),这将提高效率的运输新的 DNA 进入细胞,同时防止损坏。有前途的替代目前使用的病毒载体是基于两亲化合物的系统 - 脂质体。其中,双子表面活性剂,由两个疏水链和两个阳离子头连接的一个链接器 - 间隔基团,似乎是有前途的候选者。本研究的主题涉及两种双子表面活性剂,烷氧基衍生物的双咪唑𬭩季铵盐,在其间隔基团的长度和它们如何与两种类型的鲑鱼精子 DNA(低和高分子量(MW))或质粒 DNA(pDNA)相互作用。与核酸的不同 p/n 比(正电荷与负电荷比)的混合物被同步加速器辐射小角 X 射线散射(SAXS)、动态光散射(DLS)、圆二色性(CD)光谱学、原子力显微镜(AFM)、透射电子显微镜(TEM)和凝胶电泳技术所描绘。这种分析允许选择最适合和有前途的候选者为非病毒载体在基因治疗,确定形成稳定的复合物的条件,鉴定构象变化的 DNA 分子相互作用与双子表面活性剂和在某些情况下,确定在这些脂质体中形成的结构。

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