Journal
ACS OMEGA
Volume 4, Issue 1, Pages 819-824Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsomega.8b03139
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Funding
- National Science Centre, Poland [SYMFONIA DEC-2014/12/W/ST5/00589]
- CeNT BST funds
- Polish-U.S. Fulbright Commission
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The widespread emergence of bacterial resistance to existing antibiotics forces the development of new therapeutic agents. The use of short modified oligonucleotides, such as peptide nucleic acids (PNAs), seems a promising strategy. However, the uptake of such oligonucleotides is limited by the bacterial cell wall and is species-dependent. Therefore, new carriers for PNAs should be extensively explored. In this study, we examined the antibacterial activity of vitamin B(12-)PNA conjugates. Vitamin B-12 was covalently linked to a PNA oligomer targeted at the mRNA of an essential acpP gene encoding acyl carrier protein in Escherichia coli. PNA-vitamin B-12 conjugates were synthesized using the Cu(I)-catalyzed 1,3-dipolar cycloaddition. We examined two types of linkers between vitamin B-12 and PNA, including a cleavable disulfide bond. As a positive control for PNA uptake, we used PNA conjugated to the most widely used cell-penetrating peptide (KFF)(3)K. We found that vitamin B-12-PNA conjugates inhibit E. coli growth at a concentration of 5 mu M, similar as (KFF)(3)K-PNA. We also showed that vitamin B-12-PNA conjugates are stable in the presence of biological media. This study provides the foundation for improving and developing PNAs conjugated to vitamin B-12 as antibacterials.
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