Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-08032-8
Keywords
-
Categories
Funding
- National Science Centre [SYMFONIA DEC-2014/12/W/ST5/00589]
Ask authors/readers for more resources
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 B-12 to transport peptide nucleic acid (PNA) oligomers into cells of Escherichia coli and Salmonella Typhimurium. Vitamin B-12 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 B-12 conjugates; namely the vitamin B-12 azide was reacted with PNA possessing the terminal alkyne group. Different types of linkers and spacers between vitamin B-12 and PNA were tested, including a disulfide bond. We found that vitamin B-12 transports antisense PNA into E. coli cells more efficiently than the most widely used cellpenetrating peptide (KFF)(3)K. We also determined that the structure of the linker impacts the antisense effect. The results of this study provide the foundation for developing vitamin B-12 as a carrier of PNA oligonucleotides into bacterial cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available