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Bistable Photoswitch Allows in Vivo Control of Hematopoiesis
dc.creator | Albert, Lea | |
dc.creator | Nagpal, Jatin | |
dc.creator | Steinchen, Wieland | |
dc.creator | Zhang, Lei | |
dc.creator | Werel, Laura | |
dc.creator | Đoković, Nemanja | |
dc.creator | Ružić, Dušan | |
dc.creator | Hoffarth, Malte | |
dc.creator | Xu, Jing | |
dc.creator | Kaspareit, Johanna | |
dc.creator | Abendroth, Frank | |
dc.creator | Royant, Antoine | |
dc.creator | Bange, Gert | |
dc.creator | Nikolić, Katarina | |
dc.creator | Ryu, Soojin | |
dc.creator | Dou, Yali | |
dc.creator | Essen, Lars-Oliver | |
dc.creator | Vázquez, Olalla | |
dc.date.accessioned | 2023-07-07T12:03:15Z | |
dc.date.available | 2023-07-07T12:03:15Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 2374-7943 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/4904 | |
dc.description.abstract | Optical control has enabled functional modulation in cell culture with unparalleled spatiotemporal resolution. However, current tools for in vivo manipulation are scarce. Here, we design and implement a genuine on−of f optochemical probe capable of achieving hematopoietic control in zebrafish. Our photopharmacological approach first developed conformationally strained visible light photoswitches (CS-VIPs) as inhibitors of the histone methyltransferase MLL1 (KMT2A). In blood homeostasis MLL1 plays a crucial yet controversial role. CS-VIP 8 optimally fulfils the requirements of a true bistable functional system in vivo under visible-light irradiation, and with unprecedented stability. These properties are exemplified via hematopoiesis photoinhibition with a single isomer in zebrafish. The present interdisciplinary study uncovers the mechanism of action of CS-VIPs. Upon WDR5 binding, CS-VIP 8 causes MLL1 release with concomitant allosteric rearrangements in the WDR5/RbBP5 interface. Since our tool provides on-demand reversible control without genetic intervention or continuous irradiation, it will foster hematopathology and epigenetic investigations. Furthermore, our workflow will enable exquisite photocontrol over other targets inhibited by macrocycles. | sr |
dc.language.iso | en | sr |
dc.publisher | American Chemical Society | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200161/RS// | sr |
dc.rights | openAccess | sr |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | ACS Central Science | sr |
dc.title | Bistable Photoswitch Allows in Vivo Control of Hematopoiesis | sr |
dc.type | article | sr |
dc.rights.license | BY-NC-ND | sr |
dc.citation.volume | 8 | |
dc.citation.issue | 1 | |
dc.citation.spage | 57 | |
dc.citation.epage | 66 | |
dc.citation.rank | aM21 | |
dc.identifier.wos | 000736521400001 | |
dc.identifier.doi | 10.1021/acscentsci.1c00434 | |
dc.identifier.pmid | 35106373 | |
dc.identifier.scopus | 2-s2.0-85122339027 | |
dc.identifier.fulltext | http://farfar.pharmacy.bg.ac.rs/bitstream/id/13409/bitstream_13409.pdf | |
dc.type.version | publishedVersion | sr |