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CryoEM Structure with ATP Synthase Enables Late-Stage Diversification of Cruentaren A
dc.contributor.authorDou, Xiaozheng
dc.contributor.authorGuo, Hui
dc.contributor.authorD’Amico, Terin
dc.contributor.authorAbdallah, Leah
dc.contributor.authorSubramanian, Chitra
dc.contributor.authorPatel, Bhargav A.
dc.contributor.authorCohen, Mark
dc.contributor.authorRubinstein, John L.
dc.contributor.authorBlagg, Brian S. J.
dc.date.accessioned2023-06-01T20:52:28Z
dc.date.available2024-06-01 16:52:26en
dc.date.available2023-06-01T20:52:28Z
dc.date.issued2023-05-22
dc.identifier.citationDou, Xiaozheng; Guo, Hui; D’Amico, Terin; Abdallah, Leah; Subramanian, Chitra; Patel, Bhargav A.; Cohen, Mark; Rubinstein, John L.; Blagg, Brian S. J. (2023). "CryoEM Structure with ATP Synthase Enables Late-Stage Diversification of Cruentaren A." Chemistry – A European Journal 29(29): n/a-n/a.
dc.identifier.issn0947-6539
dc.identifier.issn1521-3765
dc.identifier.urihttps://hdl.handle.net/2027.42/176897
dc.description.abstractCruentaren A is a natural product that exhibits potent antiproliferative activity against various cancer cell lines, yet its binding site within ATP synthase remained unknown, thus limiting the development of improved analogues as anticancer agents. Herein, we report the cryogenic electron microscopy (cryoEM) structure of cruentaren A bound to ATP synthase, which allowed the design of new inhibitors through semisynthetic modification. Examples of cruentaren A derivatives include a trans-alkene isomer, which was found to exhibit similar activity to cruentaren A against three cancer cell lines as well as several other analogues that retained potent inhibitory activity. Together, these studies provide a foundation for the generation of cruentaren A derivatives as potential therapeutics for the treatment of cancer.Pattern for a new design: The cryogenic electron microscopy (cryoEM) structure of cruentaren A bound to ATP synthase is reported; it facilitated the design of new inhibitors through semisynthetic modification. Cruentaren A derivatives were developed, and a trans-alkene isomer was found to exhibit similar activity to cruentaren A against three cancer cell lines as well as other analogues that still retained potent inhibitory activity.
dc.publisherWiley Periodicals, Inc.
dc.subject.othercruentaren A
dc.subject.othernatural product
dc.subject.otherlate-stage modification
dc.subject.otherATP synthase
dc.subject.othercryoEM structure
dc.titleCryoEM Structure with ATP Synthase Enables Late-Stage Diversification of Cruentaren A
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelChemistry
dc.subject.hlbtoplevelScience
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/176897/1/chem202300262.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/176897/2/chem202300262-sup-0001-misc_information.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/176897/3/chem202300262_am.pdf
dc.identifier.doi10.1002/chem.202300262
dc.identifier.sourceChemistry – A European Journal
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dc.working.doiNOen
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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