nNOS inhibition, antimicrobial and anticancer activity of the amphibian skin peptide, citropin 1.1 and synthetic modifications

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dc.contributor.authorDoyle, J.
dc.contributor.authorBrinkworth, C.
dc.contributor.authorWegener, K.
dc.contributor.authorCarver, J.
dc.contributor.authorLlewellyn, L.
dc.contributor.authorOlver, I.
dc.contributor.authorBowie, J.
dc.contributor.authorWabnitz, P.
dc.contributor.authorTyler, M.
dc.date.issued2003
dc.descriptionThe definitive version is available at www.blackwell-synergy.com
dc.description.abstractA large number of bioactive peptides have been isolated from amphibian skin secretions. These peptides have a variety of actions including antibiotic and anticancer activities and the inhibition of neuronal nitric oxide synthase. We have investigated the structure–activity relationship of citropin 1.1, a broad-spectrum antibiotic and anticancer agent that also causes inhibition of neuronal nitric oxide synthase, by making a number of synthetically modified analogues. Citropin 1.1 has been shown previously to form an amphipathic α-helix in aqueous trifluoroethanol. The results of the structure–activity studies indicate the terminal residues are important for bacterial activity and increasing the overall positive charge, while maintaining an amphipathic distribution of residues, increases activity against Gram-negative organisms. Anticancer activity generally mirrors antibiotic activity suggesting a common mechanism of action. The N-terminal residues are important for inhibition of neuronal nitric oxide synthase, as is an overall positive charge greater than three. The structure of one of the more active synthetic modifications (A4K14-citropin 1.1) was determined in aqueous trifluoroethanol, showing that this peptide also forms an amphipathic α-helix.
dc.description.statementofresponsibilityJason Doyle, Craig S. Brinkworth, Kate L. Wegener, John A. Carver, Lyndon E. Llewellyn, Ian N. Olver, John H. Bowie, Paul A. Wabnitz, Michael J. Tyler
dc.identifier.citationThe Federation of European Biochemical Societies (FEBS) Journal, 2003; 270(6):1141-1153
dc.identifier.doi10.1046/j.1432-1033.2003.03462.x
dc.identifier.issn1742-464X
dc.identifier.issn0014-2956
dc.identifier.orcidWegener, K. [0000-0002-1562-6060]
dc.identifier.orcidOlver, I. [0000-0001-5478-1576]
dc.identifier.urihttp://hdl.handle.net/2440/17949
dc.language.isoen
dc.provenancePublished Online: 19 Feb 2003
dc.publisherBlackwell Science Ltd
dc.source.urihttps://doi.org/10.1046/j.1432-1033.2003.03462.x
dc.subjectAnimals
dc.subjectBacteria
dc.subjectPeptides
dc.subjectAntimicrobial Cationic Peptides
dc.subjectAmphibian Proteins
dc.subjectAntineoplastic Agents
dc.subjectNuclear Magnetic Resonance, Biomolecular
dc.subjectDrug Screening Assays, Antitumor
dc.subjectMicrobial Sensitivity Tests
dc.subjectProtein Conformation
dc.subjectNitric Oxide Synthase
dc.subjectNitric Oxide Synthase Type I
dc.subjectAmphibians
dc.titlenNOS inhibition, antimicrobial and anticancer activity of the amphibian skin peptide, citropin 1.1 and synthetic modifications
dc.typeJournal article
pubs.publication-statusPublished

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