Vitamin B(12) as a carrier of peptide nucleic acid (PNA) into bacterial cells.
Vitamin B(12) as a carrier of peptide nucleic acid (PNA) into bacterial cells.
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DOI：
10.1038/s41598-017-08032-8
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发表时间：
2017-08-09
影响因子：
4.6
通讯作者：
Trylska J
中科院分区：
文献类型：
--
作者：
Równicki M;Wojciechowska M;Wierzba AJ;Czarnecki J;Bartosik D;Gryko D;Trylska J
靶向细菌DNA或RNA的简短修饰的寡核苷酸可以用作抗菌剂，只要它们被细菌细胞有效地吸收。然而，这种寡核苷酸的摄取受到细菌细胞壁的阻碍。为了克服这个问题，低聚物已经连接到细胞渗透肽上，但是递送的效率仍然很差。因此，我们研究了维生素B12将肽核酸（PNA）低聚物转运到大肠杆菌和鼠伤寒沙门氏菌细胞中的能力。维生素B12与表达红色荧光蛋白的报告基因的mRNA的PNA低聚物共价链接。 Cu催化的1,3-二极环加成用于合成PNA-VITAMIN B12结合物。即维生素B12叠氮化物与具有末端藻类的PNA反应。测试了维生素B12和PNA之间的不同类型的接头和间隔，包括二硫键。我们发现，维生素B12比最广泛使用的细胞穿透肽（KFF）3K更有效地将反义PNA转运到大肠杆菌细胞中。我们还确定接头的结构会影响反义效应。这项研究的结果为开发维生素B12作为PNA寡核苷酸的载体为细菌细胞提供了基础。
Short modified oligonucleotides targeted at bacterial DNA or RNA could serve as antibacterial agents provided that they are efficiently taken up by bacterial cells. However, the uptake of such oligonucleotides is hindered by the bacterial cell wall. To overcome this problem, oligomers have been attached to cell-penetrating peptides, but the efficiency of delivery remains poor. Thus, we have investigated the ability of vitamin B12 to transport peptide nucleic acid (PNA) oligomers into cells of Escherichia coli and Salmonella Typhimurium. Vitamin B12 was covalently linked to a PNA oligomer targeted at the mRNA of a reporter gene expressing Red Fluorescent Protein. Cu-catalyzed 1,3-dipolar cycloaddition was employed for the synthesis of PNA-vitamin B12 conjugates; namely the vitamin B12 azide was reacted with PNA possessing the terminal alkyne group. Different types of linkers and spacers between vitamin B12 and PNA were tested, including a disulfide bond. We found that vitamin B12 transports antisense PNA into E. coli cells more efficiently than the most widely used cell-penetrating peptide (KFF)3K. We also determined that the structure of the linker impacts the antisense effect. The results of this study provide the foundation for developing vitamin B12 as a carrier of PNA oligonucleotides into bacterial cells.
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影响因子：
14.9
作者：
Ding, Y;Chan, CY;Lawrence, CE
通讯作者：
Lawrence, CE
影响因子：
3.7
作者：
Goh, Shan;Boberek, Jaroslaw M.;Good, Liam
通讯作者：
Good, Liam
DOI：
10.1073/pnas.77.12.7347
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DITTA, G;STANFIELD, S;HELINSKI, DR
通讯作者：
HELINSKI, DR
靶向 rpoD 基因的肽核酸的细胞穿透肽缀合物对革兰氏阴性细菌中基因表达和生长的反义抑制
影响因子：
14
作者：
Bai, Hui;You, Yu;Luo, Xiaoxing
通讯作者：
Luo, Xiaoxing
影响因子：
4.7
作者：
Hansen, Anna Mette;Bonke, Gitte;Franzyk, Henrik
通讯作者：
Franzyk, Henrik