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dc.contributor.authorLiao, Xiaoli
dc.contributor.authorRabideau, Amy E.
dc.contributor.authorPentelute, Bradley L.
dc.date.accessioned2014-09-25T16:21:42Z
dc.date.available2014-09-25T16:21:42Z
dc.date.issued2014-09
dc.date.submitted2014-06
dc.identifier.issn14394227
dc.identifier.urihttp://hdl.handle.net/1721.1/90351
dc.description.abstractAntibody mimics have significant scientific and therapeutic utility for the disruption of protein–protein interactions inside cells; however, their delivery to the cell cytosol remains a major challenge. Here we show that protective antigen (PA), a component of anthrax toxin, efficiently transports commonly used antibody mimics to the cytosol of mammalian cells when conjugated to the N-terminal domain of LF (LFN). In contrast, a cell-penetrating peptide (CPP) was not able to deliver any of these antibody mimics into the cell cytosol. The refolding and binding of a transported tandem monobody to Bcr-Abl (its protein target) in chronic myeloid leukemia cells were confirmed by co-immunoprecipitation. We also observed inhibition of Bcr-Abl kinase activity and induction of apoptosis caused by the monobody. In a separate case, we show disruption of key interactions in the MAPK signaling pathway after PA-mediated delivery of an affibody binder that targets hRaf-1. We show for the first time that PA can deliver bioactive antibody mimics to disrupt intracellular protein–protein interactions. This technology adds a useful tool to expand the applications of these modern agents to the intracellular milieu.en_US
dc.description.sponsorshipMassachusetts Institute of Technology (Startup funds)en_US
dc.description.sponsorshipMassachusetts Institute of Technology (MIT Reed Fund)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (NSF CAREER Award (CHE-1351807))en_US
dc.description.sponsorshipDamon Runyon Cancer Research Foundation (award)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (Graduate Research Fellowship)en_US
dc.language.isoen_US
dc.publisherWILEY-VCH Verlag GmbH & Co.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1002/cbic.201402290en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivativesen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceWileyen_US
dc.titleDelivery of Antibody Mimics into Mammalian Cells via Anthrax Toxin Protective Antigenen_US
dc.typeArticleen_US
dc.identifier.citationLiao, Xiaoli, Amy E. Rabideau, and Bradley L. Pentelute. “Delivery of Antibody Mimics into Mammalian Cells via Anthrax Toxin Protective Antigen.” ChemBioChem, Early view, (September 22, 2014): 10 pages.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.mitauthorLiao, Xiaolien_US
dc.contributor.mitauthorRabideau, Amy E.en_US
dc.contributor.mitauthorPentelute, Bradley L.en_US
dc.relation.journalChemBioChemen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLiao, Xiaoli; Rabideau, Amy E.; Pentelute, Bradley L.en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-2659-7012
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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