Institute of Organic Chemistry Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
Chem Commun (Camb). 2019 Jan 15;55(6):763-766. doi: 10.1039/c8cc05064c.
Specifically designed, antisense oligonucleotides are promising candidates for antibacterial drugs. They suppress the correct expression of bacterial genes by complementary binding to essential sequences of bacterial DNA or RNA. The main obstacle in fully utilizing their potential as therapeutic agents comes from the fact that bacteria do not uptake oligonucleotides from their environment. Herein, we report that vitamin B12 can transport oligonucleotides into Escherichia coli and Salmonella typhimurium cells. 5'-Aminocobalamin with an alkyne linker and azide-modified oligonucleotides enabled the synthesis of vitamin B12-2'OMeRNA conjugates using an efficient "click" methodology. Inhibition of protein expression in E. coli and S. Typhimurium cells indicates an unprecedented transport of 2'OMeRNA oligomers into bacterial cells via the vitamin B12 delivery pathway.
专门设计的反义寡核苷酸是有前途的抗菌药物候选物。它们通过与细菌 DNA 或 RNA 的必需序列互补结合来抑制细菌基因的正确表达。充分发挥其作为治疗剂的潜力的主要障碍来自于这样一个事实，即细菌不会从其环境中摄取寡核苷酸。在此，我们报告维生素 B12 可以将寡核苷酸转运到大肠杆菌和鼠伤寒沙门氏菌细胞中。带有炔基连接子和叠氮修饰的寡核苷酸的 5'-氨基钴胺素使使用高效的“点击”方法合成维生素 B12-2'OMeRNA 缀合物成为可能。大肠杆菌和鼠伤寒沙门氏菌细胞中蛋白质表达的抑制表明，2'OMeRNA 寡聚物通过维生素 B12 递药途径以前所未有的方式被转运到细菌细胞中。
