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dc.contributor.authorPassarini, Ilaria
dc.contributor.authorErnesto de Resende, Pedro
dc.contributor.authorSoares, Sarah
dc.contributor.authorTahmasi, Tadeh
dc.contributor.authorStapleton, Paul
dc.contributor.authorMalkinson, John
dc.contributor.authorZloh, Mire
dc.contributor.authorRossiter, Sharon
dc.date.accessioned2020-12-01T00:07:31Z
dc.date.available2020-12-01T00:07:31Z
dc.date.issued2020-11-30
dc.identifier.citationPassarini , I , Ernesto de Resende , P , Soares , S , Tahmasi , T , Stapleton , P , Malkinson , J , Zloh , M & Rossiter , S 2020 , ' Synthesis and in silico modelling of the potential dual mechanistic activity of small cationic peptides potentiating the antibiotic novobiocin against susceptible and multi-drug resistant Escherichia coli ' , International Journal of Molecular Sciences , vol. 21 , no. 23 , 9134 , pp. 1-19 . https://doi.org/10.3390/ijms21239134
dc.identifier.issn1422-0067
dc.identifier.otherPURE: 19036860
dc.identifier.otherPURE UUID: 852f41e8-fd43-4d6e-8fd2-c65e1fc83827
dc.identifier.otherScopus: 85096976541
dc.identifier.otherPubMed: 33266278
dc.identifier.urihttp://hdl.handle.net/2299/23527
dc.descriptionFunding Information: Funding: Tadeh Tahmasi was partially supported by a Wellcome Vacation Scholarship (202526/Z/16/Z). Pedro de Resende and Sarah Soares were supported by CAPES‐Brazil (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). Funding Information: Acknowledgments: Ilaria Passarini was supported by a University of Hertfordshire PhD studentship. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
dc.description.abstractCationic antimicrobial peptides have attracted interest, both as antimicrobial agents and for their ability to increase cell permeability to potentiate other antibiotics. However, toxicity to mammalian cells and complexity have hindered development for clinical use. We present the design and synthesis of very short cationic peptides (3-9 residues) with potential dual bacterial membrane permeation and efflux pump inhibition functionality. Peptides were designed based upon in silico similarity to known active peptides and efflux pump inhibitors. A number of these peptides potentiate the activity of the antibiotic novobiocin against susceptible Escherichia coli and restore antibiotic activity against a multi-drug resistant E. coli strain, despite having minimal or no intrinsic antimicrobial activity. Molecular modelling studies, via docking studies and short molecular dynamics simulations, indicate two potential mechanisms of potentiating activity; increasing antibiotic cell permeation via complexation with novobiocin to enable self-promoted uptake, and binding the E. coli RND efflux pump. These peptides demonstrate potential for restoring the activity of hydrophobic drugs.en
dc.format.extent19
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.rightsOpen
dc.subjectAntibiotic potentiation
dc.subjectAntimicrobial peptides
dc.subjectAntimicrobial resistance
dc.subjectDocking
dc.subjectEfflux pump inhibitor
dc.subjectMolecular dynamics
dc.subjectMolecular similarity
dc.subjectPeptide synthesis
dc.subjectCatalysis
dc.subjectMolecular Biology
dc.subjectSpectroscopy
dc.subjectComputer Science Applications
dc.subjectPhysical and Theoretical Chemistry
dc.subjectOrganic Chemistry
dc.subjectInorganic Chemistry
dc.titleSynthesis and in silico modelling of the potential dual mechanistic activity of small cationic peptides potentiating the antibiotic novobiocin against susceptible and multi-drug resistant Escherichia colien
dc.contributor.institutionDepartment of Clinical and Pharmaceutical Sciences
dc.contributor.institutionCentre for Health Services and Clinical Research
dc.contributor.institutionPsychopharmacology, Drug Misuse and Novel Psychoactive Substances Unit
dc.contributor.institutionNatural Product Chemistry and Drug Design
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Clinical, Pharmaceutical and Biological Science
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85096976541&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2020-11-30
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.3390/ijms21239134
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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