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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Susanne Kjelstrup, Paula Melo Paulon Hansen, Line E Thomsen, Paul Robert Hansen, Anders Løbner-Olesen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a1d84ef68da47b7bc1e7c24c7ee05a3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9a1d84ef68da47b7bc1e7c24c7ee05a3
record_format	dspace
spelling	oai:doaj.org-article:9a1d84ef68da47b7bc1e7c24c7ee05a32021-11-18T08:57:04ZCyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus.1932-620310.1371/journal.pone.0072273https://doaj.org/article/9a1d84ef68da47b7bc1e7c24c7ee05a32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24023733/?tool=EBIhttps://doaj.org/toc/1932-6203Interaction 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.Susanne KjelstrupPaula Melo Paulon HansenLine E ThomsenPaul Robert HansenAnders Løbner-OlesenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e72273 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Susanne Kjelstrup Paula Melo Paulon Hansen Line E Thomsen Paul Robert Hansen Anders Løbner-Olesen Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus.
description	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.
format	article
author	Susanne Kjelstrup Paula Melo Paulon Hansen Line E Thomsen Paul Robert Hansen Anders Løbner-Olesen
author_facet	Susanne Kjelstrup Paula Melo Paulon Hansen Line E Thomsen Paul Robert Hansen Anders Løbner-Olesen
author_sort	Susanne Kjelstrup
title	Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus.
title_short	Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus.
title_full	Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus.
title_fullStr	Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus.
title_full_unstemmed	Cyclic peptide inhibitors of the β-sliding clamp in Staphylococcus aureus.
title_sort	cyclic peptide inhibitors of the β-sliding clamp in staphylococcus aureus.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9a1d84ef68da47b7bc1e7c24c7ee05a3
work_keys_str_mv	AT susannekjelstrup cyclicpeptideinhibitorsofthebslidingclampinstaphylococcusaureus AT paulamelopaulonhansen cyclicpeptideinhibitorsofthebslidingclampinstaphylococcusaureus AT lineethomsen cyclicpeptideinhibitorsofthebslidingclampinstaphylococcusaureus AT paulroberthansen cyclicpeptideinhibitorsofthebslidingclampinstaphylococcusaureus AT andersløbnerolesen cyclicpeptideinhibitorsofthebslidingclampinstaphylococcusaureus
_version_	1718421156205166592

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

Ejemplares similares