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通过脂质体的DNA控制组装研究脂化聚氮杂冠醚DNA共轭物(LiNAs)的设计、合成及膜锚定强度

Design, synthesis and membrane anchoring strength of lipidated polyaza crown ether DNA-conjugates (LiNAs) studied by DNA-controlled assembly of liposomes.

作者信息

Jakobsen Ulla, Rosholm Kadla Røskva, Vogel Stefan

机构信息

University of Southern Denmark, Department of Physics, Chemistry and Pharmacy, Campusvej 55, 5230 Odense M, Denmark.

出版信息

Org Biomol Chem. 2022 Dec 7;20(47):9460-9468. doi: 10.1039/d2ob01517j.

Abstract

Hybridization-controlled assays for assembly or fusion of liposomes are versatile for detection of both DNA and RNA targets and useful for the evaluation of membrane anchoring strength of LiNAs with applications in the context of liposome assembly, liposome fusion and lipid nanoparticle formulation of therapeutic LiNAs. Herein, we report the synthesis of lipid phosphoramidite building blocks for automated LiNA synthesis and a study on design requirements for efficient lipid membrane anchoring and liposome assembly dependent on lipid membrane anchor length (C-C) and structure, the effect of internal linkers and locked nucleic acids (LNA) building blocks on the lipid membrane anchoring strength of LiNAs.

摘要

用于脂质体组装或融合的杂交控制测定法对于检测DNA和RNA靶标具有通用性,并且对于评估LiNA的膜锚定强度很有用,可应用于脂质体组装、脂质体融合以及治疗性LiNA的脂质纳米颗粒制剂。在此,我们报告了用于自动化LiNA合成的脂质亚磷酰胺构建块的合成,以及一项关于高效脂质膜锚定和脂质体组装的设计要求的研究,该要求取决于脂质膜锚定长度(C-C)和结构、内部接头和锁核酸(LNA)构建块对LiNA脂质膜锚定强度的影响。

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