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dc.contributor.authorTorres, Marcelo DT
dc.contributor.authorPedron, Cibele N
dc.contributor.authorHigashikuni, Yasutomi
dc.contributor.authorKramer, Robin M
dc.contributor.authorCardoso, Marlon H
dc.contributor.authorOshiro, Karen GN
dc.contributor.authorFranco, Octávio L
dc.contributor.authorSilva Junior, Pedro I
dc.contributor.authorSilva, Fernanda D
dc.contributor.authorOliveira Junior, Vani X
dc.contributor.authorLu, Timothy K
dc.contributor.authorde la Fuente-Nunez, Cesar
dc.date.accessioned2021-10-27T20:09:47Z
dc.date.available2021-10-27T20:09:47Z
dc.date.issued2018
dc.identifier.urihttps://hdl.handle.net/1721.1/134906
dc.description.abstract© 2018, The Author(s). Antimicrobial peptides (AMPs) constitute promising alternatives to classical antibiotics for the treatment of drug-resistant infections, which are a rapidly emerging global health challenge. However, our understanding of the structure-function relationships of AMPs is limited, and we are just beginning to rationally engineer peptides in order to develop them as therapeutics. Here, we leverage a physicochemical-guided peptide design strategy to identify specific functional hotspots in the wasp-derived AMP polybia-CP and turn this toxic peptide into a viable antimicrobial. Helical fraction, hydrophobicity, and hydrophobic moment are identified as key structural and physicochemical determinants of antimicrobial activity, utilized in combination with rational engineering to generate synthetic AMPs with therapeutic activity in a mouse model. We demonstrate that, by tuning these physicochemical parameters, it is possible to design nontoxic synthetic peptides with enhanced sub-micromolar antimicrobial potency in vitro and anti-infective activity in vivo. We present a physicochemical-guided rational design strategy to generate peptide antibiotics.
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/S42003-018-0224-2
dc.rightsCreative Commons Attribution 4.0 International license
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceNature
dc.titleStructure-function-guided exploration of the antimicrobial peptide polybia-CP identifies activity determinants and generates synthetic therapeutic candidates
dc.typeArticle
dc.contributor.departmentMassachusetts Institute of Technology. Synthetic Biology Center
dc.contributor.departmentMassachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics
dc.contributor.departmentMassachusetts Institute of Technology. Research Laboratory of Electronics
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.contributor.departmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
dc.contributor.departmentMassachusetts Institute of Technology. Division of Comparative Medicine
dc.relation.journalCommunications Biology
dc.eprint.versionFinal published version
dc.type.urihttp://purl.org/eprint/type/JournalArticle
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.date.updated2019-06-13T13:50:16Z
dspace.orderedauthorsTorres, MDT; Pedron, CN; Higashikuni, Y; Kramer, RM; Cardoso, MH; Oshiro, KGN; Franco, OL; Silva Junior, PI; Silva, FD; Oliveira Junior, VX; Lu, TK; de la Fuente-Nunez, C
dspace.date.submission2019-06-13T13:50:17Z
mit.journal.volume1
mit.journal.issue1
mit.metadata.statusAuthority Work and Publication Information Needed


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