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dc.contributor.authorFeng, Zhaoqianqi
dc.contributor.authorWang, Huaimin
dc.contributor.authorWang, ShiYu
dc.contributor.authorZhang, Qiang
dc.contributor.authorZhang, Xixiang
dc.contributor.authorRodal, Avital
dc.contributor.authorXu, Bing
dc.date.accessioned2018-08-27T08:20:16Z
dc.date.available2018-08-27T08:20:16Z
dc.date.issued2018-07-11
dc.identifier.citationFeng Z, Wang H, Wang S, Zhang Q, Zhang X, et al. (2018) Enzymatic Assemblies Disrupt the Membrane and Target Endoplasmic Reticulum for Selective Cancer Cell Death. Journal of the American Chemical Society 140: 9566–9573. Available: http://dx.doi.org/10.1021/jacs.8b04641.
dc.identifier.issn0002-7863
dc.identifier.issn1520-5126
dc.identifier.doi10.1021/jacs.8b04641
dc.identifier.urihttp://hdl.handle.net/10754/628079
dc.description.abstractThe endoplasmic reticulum (ER) is responsible for the synthesis and folding of a large number of proteins, as well as intracellular calcium regulation, lipid synthesis, and lipid transfer to other organelles, and is emerging as a target for cancer therapy. However, strategies for selectively targeting the ER of cancer cells are limited. Here we show that enzymatically generated crescent-shaped supramolecular assemblies of short peptides disrupt cell membranes and target ER for selective cancer cell death. As revealed by sedimentation assay, the assemblies interact with synthetic lipid membranes. Live cell imaging confirms that the assemblies impair membrane integrity, which is further supported by lactate dehydrogenase (LDH) assays. According to transmission electron microscopy (TEM), static light scattering (SLS), and critical micelle concentration (CMC), attaching an l-amino acid at the C-terminal of a d-tripeptide results in the crescent-shaped supramolecular assemblies. Structure-activity relationship suggests that the crescent-shaped morphology is critical for interacting with membranes and for controlling cell fate. Moreover, fluorescent imaging indicates that the assemblies accumulate on the ER. Time-dependent Western blot and ELISA indicate that the accumulation causes ER stress and subsequently activates the caspase signaling cascade for cell death. As an approach for in situ generating membrane binding scaffolds (i.e., the crescent-shaped supramolecular assemblies), this work promises a new way to disrupt the membrane and to target the ER for developing anticancer therapeutics.
dc.description.sponsorshipThis work was partially supported by the NIH (R01CA142746) and NSF (DMR-1420382).
dc.publisherAmerican Chemical Society (ACS)
dc.relation.urlhttps://pubs.acs.org/doi/10.1021/jacs.8b04641
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/jacs.8b04641.
dc.titleEnzymatic Assemblies Disrupt Membrane and Target Endoplasmic Reticulum (ER) for Selective Cancer Cell Death
dc.typeArticle
dc.contributor.departmentMaterial Science and Engineering Program
dc.contributor.departmentPhysical Science and Engineering (PSE) Division
dc.identifier.journalJournal of the American Chemical Society
dc.eprint.versionPost-print
dc.contributor.institutionDepartment of Chemistry , Brandeis University , 415 South Street , Waltham , Massachusetts 02454 , United States.
dc.contributor.institutionDepartment of Biology , Brandeis University , 415 South Street , Waltham , Massachusetts 02454 , United States.
kaust.personZhang, Qiang
kaust.personZhang, Xixiang
refterms.dateFOA2018-08-27T12:26:03Z
dc.date.published-online2018-07-11
dc.date.published-print2018-08


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