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dc.contributor.authorPassarini, Ilaria
dc.contributor.authorRossiter, Sharon
dc.contributor.authorMalkinson, John
dc.contributor.authorZloh, Mire
dc.date.accessioned2018-07-03T16:24:48Z
dc.date.available2018-07-03T16:24:48Z
dc.date.issued2018-06-21
dc.identifier.citationPassarini , I , Rossiter , S , Malkinson , J & Zloh , M 2018 , ' In silico structural evaluation of short cationic antimicrobial peptides ' , Pharmaceutics , vol. 10 , no. 3 , 72 . https://doi.org/10.3390/pharmaceutics10030072
dc.identifier.issn1999-4923
dc.identifier.otherPURE: 14886542
dc.identifier.otherPURE UUID: bbba9255-e48b-4901-ab5b-b35f016fb299
dc.identifier.otherScopus: 85049312519
dc.identifier.urihttp://hdl.handle.net/2299/20255
dc.description© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.description.abstractCationic peptides with antimicrobial properties are ubiquitous in nature and have been studied for many years in an attempt to design novel antibiotics. However, very few molecules are used in the clinic so far, sometimes due to their complexity but, mostly, as a consequence of the unfavorable pharmacokinetic profile associated with peptides. The aim of this work is to investigate cationic peptides in order to identify common structural features which could be useful for the design of small peptides or peptido-mimetics with improved drug-like properties and activity against Gram negative bacteria. Two sets of cationic peptides (AMPs) with known antimicrobial activity have been investigated. The first reference set comprised molecules with experimentally-known conformations available in the protein databank (PDB), and the second one was composed of short peptides active against Gram negative bacteria but with no significant structural information available. The predicted structures of the peptides from the first set were in excellent agreement with those experimentally-observed, which allowed analysis of the structural features of the second group using computationally-derived conformations. The peptide conformations, either experimentally available or predicted, were clustered in an “all vs. all” fashion and the most populated clusters were then analyzed. It was confirmed that these peptides tend to assume an amphipathic conformation regardless of the environment. It was also observed that positively-charged amino acid residues can often be found next to aromatic residues. Finally, a protocol was evaluated for the investigation of the behavior of short cationic peptides in the presence of a membrane-like environment such as dodecylphosphocholine (DPC) micelles. The results presented herein introduce a promising approach to inform the design of novel short peptides with a potential antimicrobial activity.en
dc.language.isoeng
dc.relation.ispartofPharmaceutics
dc.rightsOpen
dc.subjectAmphipathic conformation
dc.subjectCationic antimicrobial peptides (AMPs)
dc.subjectDodecylphosphocholine (DPC) micelles
dc.subjectMolecular dynamics
dc.subjectProtein structure prediction
dc.subjectPharmaceutical Science
dc.titleIn silico structural evaluation of short cationic antimicrobial peptidesen
dc.contributor.institutionDepartment of Pharmacy, Pharmacology and Postgraduate Medicine
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionMedicinal and Analytical Chemistry
dc.contributor.institutionNatural Product Chemistry and Drug Design
dc.contributor.institutionCentre for Health Services and Clinical Research
dc.contributor.institutionDepartment of Clinical and Pharmaceutical Sciences
dc.contributor.institutionPsychopharmacology, Drug Misuse and Novel Psychoactive Substances Unit
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85049312519&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2018-06-21
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.3390/pharmaceutics10030072
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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