Antibacterial Peptide Nucleic Acids—Facts and Perspectives
Abstract
:1. Introduction
2. PNA Complexes with Natural Nucleic Acids
3. Chemical Modifications of PNA
4. Delivery of PNA to Bacteria
5. Applications of PNA as an Antibacterial Agent
5.1. Targeting the mRNA of Essential Genes with Antisense PNA
5.2. Ribosome as a Target for Antibacterial PNA
5.3. Other mRNA Targets
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Molecule | Structure | Method | Resolution | Includes Modified PNA Monomers | PDB ID | Ref. |
---|---|---|---|---|---|---|
PNA-PNA | duplex | X-ray | 1.82 Å | bicyclic thymine analogue | 1HZS | [20] |
duplex | NMR | - | - | 2K4G | [21] | |
duplex | X-ray | 1.70 Å | - | 1PUP | [22] | |
duplex | X-ray | 2.35 Å | - | 1RRU | [23] | |
duplex/triplex | X-ray | 2.60 Å | - | 1XJ9 | [24] | |
duplex | NMR | - | γ-modified PNA | 2KVJ | [25] | |
duplex | X-ray | 1.27 Å | - | 3MBS | [26] | |
duplex | X-ray | 2.20 Å | N-methylated PNA backbone | 1QPY | [27] | |
duplex | X-ray | 1.05 Å | bipyridine-modified PNA | 3MBU | [26] | |
duplex | X-ray | 1.06 Å | contains T-T mismatches | 5EMG | [28] | |
PNA | single-stranded PNA | X-ray | 1.00 Å | d-alanyl and l-homoalanyl PNA | 3C1P | [29] |
PNA-RNA | duplex | NMR | - | - | 176D | [30] |
duplex | X-ray | 1.15 Å | - | 5EME | [28] | |
duplex | X-ray | 1.14 Å | - | 5EMF | [28] | |
PNA-DNA | duplex | NMR | - | - | 1PDT | [31] |
duplex | X-ray | 1.66 Å | d-Lys based PNA | 1NR8 | [32] | |
duplex | X-ray | 1.60 Å | γ-modified PNA | 3PA0 | [33] | |
PNA-DNA-PNA | triplex | X-ray | 2.50 Å | HIS-GLY-SER-SER-GLY-HIS-linker | 1PNN | [34] |
Target | Function | Bacteria | MIC * (μM) | Reference |
---|---|---|---|---|
mRNA of essential genes | ||||
acpP | fatty acid biosynthesis | Brucella suis 1330 | 30 ** | [128] |
Escherichia coli K-12 | 0.6 | [11] | ||
Haemophilus influenza | 0.6 | [129] | ||
Pseudomonas aeruginosa PAO1 | 2 | [130] | ||
hmrB | Staphylococcus aureus RN4220 | 10 | [122] | |
fabI | Escherichia coli K-12 | 3 | [131] | |
Staphylococcus aureus RN4220 | 15 | |||
folA | folate biosynthesis | Escherichia coli AS19 | 2.5 | |
folP | Escherichia coli AS19 | 2.5 | ||
gyrA | DNA replication | Acinetobacter baumanii CY-623 | 5 | [147] |
Brucella suis 1330 | 30 | [128] | ||
Klebsiella pneumoniae | 20 | [148] | ||
Staphylococcus aureus RN4220 | 10 | [131] | ||
Streptococcus pyogenes | [111] | |||
rpoD | DNA transcription | Escherichia coli (ESBL+) | 6.2 | [110] |
Klebsiella pneumoniae (ESBL+) | 30 | [110] | ||
Listeria monocytogenes ATCC 19114 | 2 *** | [112] | ||
Salmonella enterica serovar Typhimurium LT2 | 15 *** | [149] | ||
Shigella flexneri (MDR) | 5 | [110] | ||
Staphylococcus aureus ATCC29213 | 6.2 | [108] | ||
murA | cell-wall biogenesis | Escherichia coli DH10B | 2.4 | [134] |
Klebsiella pneumoniae ATCC 700721 | 2.5 | |||
Salmonella enterica serovar Typhimurium LT2 | 1.2 | |||
ftsZ | cell division | Bacillus subtilis 168 | 4 | [134] |
Salmonella enterica serovar Typhimurium LT2 | 2.5 | |||
inhA | mycolic acid biosynthesis | Mycobacterium smegmatis 155 | <5 | [133] |
rRNA | ||||
PTC | peptidyl transferase center 23S rRNA | Escherichia coli K-12 | 50 *** | [137] |
a-sarcin loop | binds elongation factor G (EF-G) 23S rRNA | Escherichia coli K-12 | 50 *** | |
Helix 69 | forms connection between ribosomal subunits | Escherichia coli K-12 | 15 | [139] |
mRBS | mRNA binding site 16S rRNA | Corynebacterium efficiens | 2 | [140] |
Bacillus subtilis | 5 | |||
Escherichia coli K-12 | 10 | |||
830−839 16S RNA | part of IF3 binding site 16S rRNA | Escherichia coli K-12 | 15 | [142] |
830−839 16S RNA | part of IF3 binding site 16S rRNA | Salmonella enterica serovar Typhimurium LT2 | 5 | |
Other mRNA targets | ||||
motA | biofilm formation | Pseudomonas aeruginosa PAO1 | 1 | [143] |
cmeABC | multidrug efflux transporter | Campylobacter jejuni | - | [145] |
mazE | antitoxin MazE | Escherichia coli WR3551/98 | 16 | [146] |
hipB | antitoxin HipB | Escherichia coli WR3551/98 | 16 | |
thyA | thymidylate synthase | Escherichia coli WR3551/98 | 16 | |
gltX | glutamyl-tRNA synthetase | Escherichia coli WR3551/98 | 2 |
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Wojciechowska, M.; Równicki, M.; Mieczkowski, A.; Miszkiewicz, J.; Trylska, J. Antibacterial Peptide Nucleic Acids—Facts and Perspectives. Molecules 2020, 25, 559. https://doi.org/10.3390/molecules25030559
Wojciechowska M, Równicki M, Mieczkowski A, Miszkiewicz J, Trylska J. Antibacterial Peptide Nucleic Acids—Facts and Perspectives. Molecules. 2020; 25(3):559. https://doi.org/10.3390/molecules25030559
Chicago/Turabian StyleWojciechowska, Monika, Marcin Równicki, Adam Mieczkowski, Joanna Miszkiewicz, and Joanna Trylska. 2020. "Antibacterial Peptide Nucleic Acids—Facts and Perspectives" Molecules 25, no. 3: 559. https://doi.org/10.3390/molecules25030559