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• W2111998971 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." @default.
• W2111998971 created "2016-06-24" @default.
• W2111998971 creator A5021760386 @default.
• W2111998971 creator A5056470805 @default.
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• W2111998971 date "2014-09-22" @default.
• W2111998971 modified "2023-10-12" @default.
• W2111998971 title "Delivery of Antibody Mimics into Mammalian Cells via Anthrax Toxin Protective Antigen" @default.
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• W2111998971 doi "https://doi.org/10.1002/cbic.201402290" @default.
• W2111998971 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4498471" @default.
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• W2111998971 hasPublicationYear "2014" @default.
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