dc.contributor.author | Passarini, Ilaria | |
dc.contributor.author | Ernesto de Resende, Pedro | |
dc.contributor.author | Soares, Sarah | |
dc.contributor.author | Tahmasi, Tadeh | |
dc.contributor.author | Stapleton, Paul | |
dc.contributor.author | Malkinson, John | |
dc.contributor.author | Zloh, Mire | |
dc.contributor.author | Rossiter, Sharon | |
dc.date.accessioned | 2020-12-01T00:07:31Z | |
dc.date.available | 2020-12-01T00:07:31Z | |
dc.date.issued | 2020-11-30 | |
dc.identifier.citation | Passarini , 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 (IJMS) , vol. 21 , no. 23 , 9134 , pp. 1-19 . https://doi.org/10.3390/ijms21239134 | |
dc.identifier.issn | 1661-6596 | |
dc.identifier.other | ORCID: /0000-0003-3822-0028/work/142009563 | |
dc.identifier.uri | http://hdl.handle.net/2299/23527 | |
dc.description | Funding 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.abstract | Cationic 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.extent | 19 | |
dc.format.extent | 2282900 | |
dc.language.iso | eng | |
dc.relation.ispartof | International Journal of Molecular Sciences (IJMS) | |
dc.subject | Antibiotic potentiation | |
dc.subject | Antimicrobial peptides | |
dc.subject | Antimicrobial resistance | |
dc.subject | Docking | |
dc.subject | Efflux pump inhibitor | |
dc.subject | Molecular dynamics | |
dc.subject | Molecular similarity | |
dc.subject | Peptide synthesis | |
dc.subject | Catalysis | |
dc.subject | Molecular Biology | |
dc.subject | Spectroscopy | |
dc.subject | Computer Science Applications | |
dc.subject | Physical and Theoretical Chemistry | |
dc.subject | Organic Chemistry | |
dc.subject | Inorganic Chemistry | |
dc.title | 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 | en |
dc.contributor.institution | Department of Clinical and Pharmaceutical Sciences | |
dc.contributor.institution | Centre for Health Services and Clinical Research | |
dc.contributor.institution | Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Unit | |
dc.contributor.institution | Natural Product Chemistry and Drug Design | |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.description.status | Peer reviewed | |
dc.identifier.url | http://www.scopus.com/inward/record.url?scp=85096976541&partnerID=8YFLogxK | |
rioxxterms.versionofrecord | 10.3390/ijms21239134 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |