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Inhibition of Escherichia coli Growth by Vitamin B12–Peptide Nucleic Acid Conjugates

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dc.abstract.enThe 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 B12–PNA conjugates. Vitamin B12 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 B12 conjugates were synthesized using the Cu(I)-catalyzed 1,3-dipolar cycloaddition. We examined two types of linkers between vitamin B12 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)3K. We found that vitamin B12–PNA conjugates inhibit E. coli growth at a concentration of 5 μM, similar as (KFF)3K–PNA. We also showed that vitamin B12–PNA conjugates are stable in the presence of biological media. This study provides the foundation for improving and developing PNAs conjugated to vitamin B12 as antibacterials.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorDąbrowska, Zofia
dc.contributor.authorTrylska, Joanna
dc.contributor.authorWierzba, Aleksandra
dc.contributor.authorWojciechowska, Monika
dc.contributor.authorRównicki, Marcin
dc.contributor.authorGRYKO, Dorota
dc.contributor.authorMaximova, Ksenia
dc.date.accessioned2024-01-25T04:14:42Z
dc.date.available2024-01-25T04:14:42Z
dc.date.copyright2019-01-10
dc.date.issued2019
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number1
dc.description.versionFINAL_PUBLISHED
dc.description.volume4
dc.identifier.doi10.1021/ACSOMEGA.8B03139
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/109315
dc.identifier.weblinkhttps://doi.org/10.1021/acsomega.8b03139
dc.languageeng
dc.pbn.affiliationphysical sciences
dc.relation.ispartofACS Omega
dc.relation.pages819-824
dc.rightsOther
dc.sciencecloudnosend
dc.titleInhibition of Escherichia coli Growth by Vitamin B12–Peptide Nucleic Acid Conjugates
dc.typeJournalArticle
dspace.entity.typePublication