Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus. / Kjelstrup, Susanne; Hansen, Paula Melo Paulon; Thomsen, Line Elnif; Hansen, Paul Robert; Løbner-Olesen, Anders.

In: P L o S One, Vol. 8, No. 9, e72273, 2013.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Kjelstrup, S, Hansen, PMP, Thomsen, LE, Hansen, PR & Løbner-Olesen, A 2013, 'Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus', P L o S One, vol. 8, no. 9, e72273. https://doi.org/10.1371/journal.pone.0072273

APA

Kjelstrup, S., Hansen, P. M. P., Thomsen, L. E., Hansen, P. R., & Løbner-Olesen, A. (2013). Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus. P L o S One, 8(9), [e72273]. https://doi.org/10.1371/journal.pone.0072273

Vancouver

Kjelstrup S, Hansen PMP, Thomsen LE, Hansen PR, Løbner-Olesen A. Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus. P L o S One. 2013;8(9). e72273. https://doi.org/10.1371/journal.pone.0072273

Author

Kjelstrup, Susanne ; Hansen, Paula Melo Paulon ; Thomsen, Line Elnif ; Hansen, Paul Robert ; Løbner-Olesen, Anders. / Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus. In: P L o S One. 2013 ; Vol. 8, No. 9.

Bibtex

@article{7406192dc7a8424986df2f3728fa83f2,
title = "Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus",
abstract = "Interaction between pairs of Staphylococcus aureus replication proteins was detected in an Escherichia coli based two-hybrid analysis. A reverse two-hybrid system was constructed for selection of compounds that hindered interaction between interacting protein pairs. A number of cyclic peptides, from a library generated by the split intein-mediated circular ligation of peptides and proteins technology, were found to interfere with dimerization of the β-sliding clamp of the replisome. Two 8-mer peptides were analyzed in more detail. Both inhibited DNA replication, led to SOS induction, altered cell morphology and cell death. The peptides were active when added to bacterial cultures indicating that they could traverse the bacterial membrane to find their intracellular target. Peptide specificity was confirmed by overproduction of the putative target (DnaN) which resulted in resistance. The minimum inhibitory concentration was ∼50 μg/ml for S. aureus cells. These compounds may serve as lead candidates for future development into novel classes of antibiotics as well as provide information on the function of the S. aureus replication process.",
author = "Susanne Kjelstrup and Hansen, {Paula Melo Paulon} and Thomsen, {Line Elnif} and Hansen, {Paul Robert} and Anders L{\o}bner-Olesen",
note = "OA",
year = "2013",
doi = "10.1371/journal.pone.0072273",
language = "English",
volume = "8",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

RIS

TY - JOUR

T1 - Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus

AU - Kjelstrup, Susanne

AU - Hansen, Paula Melo Paulon

AU - Thomsen, Line Elnif

AU - Hansen, Paul Robert

AU - Løbner-Olesen, Anders

N1 - OA

PY - 2013

Y1 - 2013

N2 - Interaction between pairs of Staphylococcus aureus replication proteins was detected in an Escherichia coli based two-hybrid analysis. A reverse two-hybrid system was constructed for selection of compounds that hindered interaction between interacting protein pairs. A number of cyclic peptides, from a library generated by the split intein-mediated circular ligation of peptides and proteins technology, were found to interfere with dimerization of the β-sliding clamp of the replisome. Two 8-mer peptides were analyzed in more detail. Both inhibited DNA replication, led to SOS induction, altered cell morphology and cell death. The peptides were active when added to bacterial cultures indicating that they could traverse the bacterial membrane to find their intracellular target. Peptide specificity was confirmed by overproduction of the putative target (DnaN) which resulted in resistance. The minimum inhibitory concentration was ∼50 μg/ml for S. aureus cells. These compounds may serve as lead candidates for future development into novel classes of antibiotics as well as provide information on the function of the S. aureus replication process.

AB - Interaction between pairs of Staphylococcus aureus replication proteins was detected in an Escherichia coli based two-hybrid analysis. A reverse two-hybrid system was constructed for selection of compounds that hindered interaction between interacting protein pairs. A number of cyclic peptides, from a library generated by the split intein-mediated circular ligation of peptides and proteins technology, were found to interfere with dimerization of the β-sliding clamp of the replisome. Two 8-mer peptides were analyzed in more detail. Both inhibited DNA replication, led to SOS induction, altered cell morphology and cell death. The peptides were active when added to bacterial cultures indicating that they could traverse the bacterial membrane to find their intracellular target. Peptide specificity was confirmed by overproduction of the putative target (DnaN) which resulted in resistance. The minimum inhibitory concentration was ∼50 μg/ml for S. aureus cells. These compounds may serve as lead candidates for future development into novel classes of antibiotics as well as provide information on the function of the S. aureus replication process.

U2 - 10.1371/journal.pone.0072273

DO - 10.1371/journal.pone.0072273

M3 - Journal article

VL - 8

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 9

M1 - e72273

ER -

ID: 50863792