dc.contributor.author | Liao, Xiaoli | |
dc.contributor.author | Rabideau, Amy E. | |
dc.contributor.author | Pentelute, Bradley L. | |
dc.date.accessioned | 2014-09-25T16:21:42Z | |
dc.date.available | 2014-09-25T16:21:42Z | |
dc.date.issued | 2014-09 | |
dc.date.submitted | 2014-06 | |
dc.identifier.issn | 14394227 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/90351 | |
dc.description.abstract | Antibody 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.sponsorship | Massachusetts Institute of Technology (Startup funds) | en_US |
dc.description.sponsorship | Massachusetts Institute of Technology (MIT Reed Fund) | en_US |
dc.description.sponsorship | National Science Foundation (U.S.) (NSF CAREER Award (CHE-1351807)) | en_US |
dc.description.sponsorship | Damon Runyon Cancer Research Foundation (award) | en_US |
dc.description.sponsorship | National Science Foundation (U.S.) (Graduate Research Fellowship) | en_US |
dc.language.iso | en_US | |
dc.publisher | WILEY-VCH Verlag GmbH & Co. | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1002/cbic.201402290 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivatives | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | Wiley | en_US |
dc.title | Delivery of Antibody Mimics into Mammalian Cells via Anthrax Toxin Protective Antigen | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Liao, 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.department | Massachusetts Institute of Technology. Department of Chemistry | en_US |
dc.contributor.mitauthor | Liao, Xiaoli | en_US |
dc.contributor.mitauthor | Rabideau, Amy E. | en_US |
dc.contributor.mitauthor | Pentelute, Bradley L. | en_US |
dc.relation.journal | ChemBioChem | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Liao, Xiaoli; Rabideau, Amy E.; Pentelute, Bradley L. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-2659-7012 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |