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含寡核苷酸的 2'-O-[(4,5',8-三甲氧基补骨脂素)-4'-基甲氧基乙氨基羰基]腺苷的合成与评价作为光交联基因靶向工具。

Synthesis and Evaluation of Oligonucleotide-Containing 2'-O-{[(4,5',8-Trimethylpsoralen)-4'-ylmethoxy]ethylaminocarb-onyl}adenosine as Photo-crosslinkable Gene Targeting Tools.

机构信息

Graduate School of Biomedical Sciences, Nagasaki University.

SANKEN (The Institute of Scientific and Industrial Research), Osaka University.

出版信息

Chem Pharm Bull (Tokyo). 2022 Oct 1;70(10):726-730. doi: 10.1248/cpb.c22-00333. Epub 2022 Jul 28.

DOI:10.1248/cpb.c22-00333
PMID:35896347
Abstract

Several psoralen-conjugated oligonucleotides (Ps-Oligos) have been developed as photo-crosslinkable oligonucleotides targeting DNA or RNA. To avoid potential off-target effects, it is important to investigate the selective photo-crosslinking reactivity of Ps-Oligos to DNA or RNA. However, the selectivity of these Ps-Oligos has not been reported in detail thus far. In this study, we evaluated the photo-crosslinking properties of two Ps-Oligos, 5'-Ps-Oligo and a novel Ps-Oligo containing 2'-O-{[(4,5',8-trimethylpsoralen)-4'-ylmethoxy]ethylaminocarbonyl}adenosine (APs2-Oligo). Notably, 5'-Ps-Oligo preferentially crosslinked with DNA, whereas APs2-Oligo preferentially crosslinked with RNA. These results demonstrate the interesting crosslinking properties of Ps-Oligos, which will provide useful information for the molecular design of novel Ps-Oligos in future studies.

摘要

几种补骨脂素偶联寡核苷酸(Ps-Oligos)已被开发为针对 DNA 或 RNA 的光交联寡核苷酸。为了避免潜在的脱靶效应,研究 Ps-Oligos 与 DNA 或 RNA 的选择性光交联反应性非常重要。然而,迄今为止,这些 Ps-Oligos 的选择性尚未详细报道。在这项研究中,我们评估了两种 Ps-Oligos,即 5'-Ps-Oligo 和一种新型含有 2'-O-[[(4,5',8-三甲氧基补骨脂素)-4'-基甲氧基]乙氨基羰基]腺苷(APs2-Oligo)的 Ps-Oligo 的光交联性质。值得注意的是,5'-Ps-Oligo 优先与 DNA 交联,而 APs2-Oligo 优先与 RNA 交联。这些结果表明 Ps-Oligos 具有有趣的交联性质,这将为未来研究中新型 Ps-Oligos 的分子设计提供有用信息。

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