Show simple item record

dc.contributor.authorSarıyar Akbulut, Berna
dc.date.accessioned2016-04-10T11:15:30Z
dc.date.available2016-04-10T11:15:30Z
dc.date.issued2015
dc.identifier.issn10752617
dc.identifier.urihttp://tinyurl.com/hbyqyne
dc.identifier.urihttp://hdl.handle.net/11424/4356
dc.description.abstractBeta-lactamase-mediated bacterial drug resistance exacerbates the prognosis of infectious diseases, which are sometimes treated with co-administration of beta-lactam type antibiotics and beta-lactamase inhibitors. Antimicrobial peptides are promising broad-spectrum alternatives to conventional antibiotics in this era of evolving bacterial resistance. Peptides based on the Ala46-Tyr51 beta-hairpin loop of beta-lactamase inhibitory protein (BLIP) have been previously shown to inhibit beta-lactamase. Here, our goal was to modify this peptide for improved beta-lactamase inhibition and cellular uptake. Motivated by the cell-penetrating pVEC sequence, which includes a hydrophobic stretch at its N-terminus, our approach involved the addition of LLIIL residues to the inhibitory peptide N-terminus to facilitate uptake. Activity measurements of the peptide based on the 45-53 loop of BLIP for enhanced inhibition verified that the peptide was a competitive beta-lactamase inhibitor with a Ki value of 58 μM. Incubation of beta-lactam-resistant cells with peptide decreased the number of viable cells, while it had no effect on beta-lactamase-free cells, indicating that this peptide had antimicrobial activity via beta-lactamase inhibition. To elucidate the molecular mechanism by which this peptide moves across the membrane, steered molecular dynamics simulations were carried out. We propose that addition of hydrophobic residues to the N-terminus of the peptide affords a promising strategy in the design of novel antimicrobial peptides not only against beta-lactamase but also for other intracellular targets. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.en_US
dc.language.isoengen_US
dc.relation.isversionof10.1002/psc.2739en_US
dc.rightsinfo:eu-repo/semantics/restrictedAccessen_US
dc.subjectantibiotic resistance; antimicrobial peptide; beta-lactamase; cell-penetrating peptide; deliveryen_US
dc.titleA novel chimeric peptide with antimicrobial activityen_US
dc.typearticleen_US
dc.contributor.authorIDTR189139en_US
dc.relation.journalJournal of Peptide Scienceen_US
dc.contributor.departmentBioengineering Department, Marmara Universityen_US
dc.identifier.volume21en_US
dc.identifier.issue4en_US
dc.identifier.startpage294en_US
dc.identifier.endpage301en_US


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record