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 specific

SUBMITTER: Kjelstrup S 

PROVIDER: S-EPMC3762901 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature