Show simple item record

dc.contributor.authorHowl, John
dc.contributor.authorHowl, Lewis
dc.contributor.authorJones, Sarah
dc.date.accessioned2018-02-01T12:39:50Z
dc.date.available2018-02-01T12:39:50Z
dc.date.issued2018-01-11
dc.identifier.citationHowl .J, Howl L., Jones S. (2018) 'The cationic tetradecapeptide mastoparan as a privileged structure for drug discovery: Enhanced antimicrobial properties of mitoparan analogues modified at position-14', Peptides, 101 pp. 95-105. doi: 10.1016/j.peptides.2018.01.007
dc.identifier.issn0196-9781
dc.identifier.doi10.1016/j.peptides.2018.01.007
dc.identifier.urihttp://hdl.handle.net/2436/621066
dc.description.abstractMastoparan (MP) peptides, distributed in insect venoms, induce a local inflammatory response post envenomation. Most endogenous MPs share common structural elements within a tetradecapeptide sequence that adopts an amphipathic helix whilst traversing biological membranes and when bound to an intracellular protein target. Rational modifications to increase cationic charge density and amphipathic helicity engineered mitoparan (MitP), a mitochondriotoxic bioportide and potent secretagogue. Following intracellular translocation, MitP is accreted by mitochondria thus indicating additional utility as an antimicrobial agent. Hence, the objectives of this study were to compare the antimicrobial activities of a structurally diverse set of cationic cell penetrating peptides, including both MP and MitP sequences, and to chemically engineer analogues of MitP for potential therapeutic applications. Herein, we confirm that, like MP, MitP is a privileged structure for the development of antimicrobial peptides active against both prokaryotic and eukaryotic pathogens. Collectively, MitP and target-selective chimeric analogues are broad spectrum antibiotics, with the Gram-negative A. baumannii demonstrating particular susceptibility. Modifications of MitP by amino acid substitution at position-14 produced peptides, Δ14MitP analogues, with unique pharmacodynamic properties. One example, [Ser14]MitP, lacks both cytotoxicity against human cell lines and mast cell secretory activity yet retains selective activity against the encapsulated yeast C. neoformans.
dc.language.isoen
dc.publisherElsevier
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0196978118300135
dc.subjectMastoparan
dc.subjectMitoparan
dc.subjectAntimicrobial
dc.subjectAntifungal
dc.subjectCell penetrating peptide
dc.titleThe cationic tetradecapeptide mastoparan as a privileged structure for drug discovery: Enhanced antimicrobial properties of mitoparan analogues modified at position-14
dc.typeJournal article
dc.identifier.journalPeptides
dc.date.accepted2018-01-10
rioxxterms.funderUniversity of Wolverhampton
rioxxterms.identifier.projectUoW010218SJ
rioxxterms.versionAM
rioxxterms.licenseref.urihttps://creativecommons.org/CC BY-NC-ND 4.0
rioxxterms.licenseref.startdate2019-01-11
dc.source.volume101
dc.source.beginpage95
dc.source.endpage105
refterms.dateFCD2018-10-19T09:26:31Z
refterms.versionFCDAM
refterms.dateFOA2019-03-01T00:00:00Z
html.description.abstractMastoparan (MP) peptides, distributed in insect venoms, induce a local inflammatory response post envenomation. Most endogenous MPs share common structural elements within a tetradecapeptide sequence that adopts an amphipathic helix whilst traversing biological membranes and when bound to an intracellular protein target. Rational modifications to increase cationic charge density and amphipathic helicity engineered mitoparan (MitP), a mitochondriotoxic bioportide and potent secretagogue. Following intracellular translocation, MitP is accreted by mitochondria thus indicating additional utility as an antimicrobial agent. Hence, the objectives of this study were to compare the antimicrobial activities of a structurally diverse set of cationic cell penetrating peptides, including both MP and MitP sequences, and to chemically engineer analogues of MitP for potential therapeutic applications. Herein, we confirm that, like MP, MitP is a privileged structure for the development of antimicrobial peptides active against both prokaryotic and eukaryotic pathogens. Collectively, MitP and target-selective chimeric analogues are broad spectrum antibiotics, with the Gram-negative A. baumannii demonstrating particular susceptibility. Modifications of MitP by amino acid substitution at position-14 produced peptides, Δ14MitP analogues, with unique pharmacodynamic properties. One example, [Ser14]MitP, lacks both cytotoxicity against human cell lines and mast cell secretory activity yet retains selective activity against the encapsulated yeast C. neoformans.


Files in this item

Thumbnail
Name:
Publisher version
Thumbnail
Name:
proof.pdf
Size:
1.927Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

https://creativecommons.org/CC BY-NC-ND 4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/CC BY-NC-ND 4.0