MGB聚酰胺-寡核苷酸偶联物基因表达控制化合物的合成与评价。

IF 1.3 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kazuo Kamaike, Mutsumi Sano, Daisuke Sakata, Yu Nishihara, Hiroaki Amino, Akihiro Ohtsuki, Yui Okada, Takafumi Miyakawa, Makoto Kogawara, Mai Tsutsumi, Misato Takahashi, Etsuko Kawashima, Koichiro Ota, Hiroaki Miyaoka
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引用次数: 1

摘要

利用氨基烷基连接物合成了在鸟嘌呤碱基2外环氨基上连接MGB聚酰胺的MGB聚酰胺寡核苷酸偶联物ON 1-4,并利用T - m和CD分析对含有MGB聚酰胺结合序列的互补DNA的结合亲和力进行了评价。MGB聚酰胺包括对A-T碱基对具有结合亲和力的吡咯聚酰胺(Py4-和Py3-),以及对C-G碱基对具有结合亲和力的咪唑(Im3-)和吡咯-γ-咪唑(Py3-γ-Im3-)聚酰胺发夹基序。结果表明,修饰后的dsDNA的稳定性受连接体长度的影响较大。含有4-氨基丁基连接体的Py4-和py3寡核苷酸偶联物(ON 1 (n = 4)和ON 2 (n = 4))与互补DNA形成稳定的双链DNA。尽管Im3-oligonucleotide共轭3 (n = 4)包含4-aminobutyl链接器形成稳定dsDNA互补DNA,稳定的dsDNA咪唑酰胺的一部分(n = 4) 3日与吡咯酰胺相比低一半的2 (n = 4)。Py3 -γ-Im3-oligonucleotide共轭4日(n = 2),具有亲和力的c g碱基对通过吡咯/咪唑组合包含2-aminoethyl链接器,显示高绑定能力互补的DNA。此外,利用在MGB聚酰胺结合序列中具有错配碱基的单碱基错配DNA,研究了MGB聚酰胺-寡核苷酸偶联物的DNA序列识别。Py3-γ- im3寡核苷酸偶联物on4 (n = 2)对互补DNA具有较高的序列识别能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds.

MGB polyamide-oligonucleotide conjugates ON 1-4 with linked MGB polyamides at the 2-exocyclic amino group of a guanine base using aminoalkyl linkers were synthesized and evaluated in terms of binding affinity for complementary DNA containing the MGB polyamide binding sequence using T m and CD analyses. The MGB polyamides comprised pyrrole polyamides (Py4- and Py3-), which possess binding affinity for A-T base pairs, and imidazole (Im3-) and pyrrole-γ-imidazole (Py3-γ-Im3-) polyamide hairpin motifs, which possess binding affinity for C-G base pairs. It was found that the stability of modified dsDNA was greatly influenced by the linker length. Py4- and Py3-oligonucleotide conjugates (ON 1 (n = 4) and ON 2 (n = 4)) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA. Although Im3-oligonucleotide conjugate ON 3 (n = 4) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA, stabilization of dsDNA by the imidazole amide moiety of ON 3 (n = 4) was lower compared with the pyrrole amide moiety of ON 2 (n = 4). The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2), which possesses binding affinity for C-G base pairs via a pyrrole/imidazole combination and contains a 2-aminoethyl linker, showed high binding ability for complementary DNA. Furthermore, the DNA sequence recognition of MGB polyamide-oligonucleotide conjugates was investigated using single-base mismatch DNAs, which possess a mismatch base in the MGB polyamide binding sequence. The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2) showed high sequence recognition ability for complementary DNA.

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来源期刊
Journal of Nucleic Acids
Journal of Nucleic Acids BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
3.10
自引率
21.70%
发文量
5
审稿时长
12 weeks
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