Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in Escherichia coli
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Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in Escherichia coli. / Campion, Christopher; Charbon, Godefroid; Nielsen, Peter E.; Løbner-Olesen, Anders.
In: Frontiers in Antibiotics, Vol. 3, 1384390, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in Escherichia coli
AU - Campion, Christopher
AU - Charbon, Godefroid
AU - Nielsen, Peter E.
AU - Løbner-Olesen, Anders
PY - 2024
Y1 - 2024
N2 - Initiation of chromosome replication is an essential stage of the bacterial cell cycle that is controlled by the DnaA protein. With the aim of developing novel antimicrobials, we have targeted the initiation of DNA replication, using antisense peptide nucleic acids (PNAs), directed against DnaA translation. A series of anti-DnaA PNA conjugated to lysine-rich bacterial penetrating peptides (PNA-BPPs) were designed to block DnaA translation. These anti-DnaA PNA-BPPs inhibited growth of wild-type Escherichia coli cells at low micromolar concentrations, and cells exposed to anti-DnaA PNA-BPPs exhibited characteristic hallmarks of chromosome replication inhibition. These results present one of very few compounds successfully targeting initiation of chromosome replication, an essential step in the bacterial cell cycle.
AB - Initiation of chromosome replication is an essential stage of the bacterial cell cycle that is controlled by the DnaA protein. With the aim of developing novel antimicrobials, we have targeted the initiation of DNA replication, using antisense peptide nucleic acids (PNAs), directed against DnaA translation. A series of anti-DnaA PNA conjugated to lysine-rich bacterial penetrating peptides (PNA-BPPs) were designed to block DnaA translation. These anti-DnaA PNA-BPPs inhibited growth of wild-type Escherichia coli cells at low micromolar concentrations, and cells exposed to anti-DnaA PNA-BPPs exhibited characteristic hallmarks of chromosome replication inhibition. These results present one of very few compounds successfully targeting initiation of chromosome replication, an essential step in the bacterial cell cycle.
U2 - 10.3389/frabi.2024.1384390
DO - 10.3389/frabi.2024.1384390
M3 - Journal article
VL - 3
JO - Frontiers in Antibiotics
JF - Frontiers in Antibiotics
SN - 2813-2467
M1 - 1384390
ER -
ID: 387827057