Bistable Photoswitch Allows in Vivo Control of Hematopoiesis
Аутори
Albert, LeaNagpal, Jatin
Steinchen, Wieland
Zhang, Lei
Werel, Laura
Đoković, Nemanja
Ružić, Dušan
Hoffarth, Malte
Xu, Jing
Kaspareit, Johanna
Abendroth, Frank
Royant, Antoine
Bange, Gert
Nikolić, Katarina
Ryu, Soojin
Dou, Yali
Essen, Lars-Oliver
Vázquez, Olalla
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 inte...rface. 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.
Извор:
ACS Central Science, 2022, 8, 1, 57-66Издавач:
- American Chemical Society
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
DOI: 10.1021/acscentsci.1c00434
ISSN: 2374-7943
PubMed: 35106373
WoS: 000736521400001
Scopus: 2-s2.0-85122339027
Институција/група
PharmacyTY - JOUR AU - Albert, Lea AU - Nagpal, Jatin AU - Steinchen, Wieland AU - Zhang, Lei AU - Werel, Laura AU - Đoković, Nemanja AU - Ružić, Dušan AU - Hoffarth, Malte AU - Xu, Jing AU - Kaspareit, Johanna AU - Abendroth, Frank AU - Royant, Antoine AU - Bange, Gert AU - Nikolić, Katarina AU - Ryu, Soojin AU - Dou, Yali AU - Essen, Lars-Oliver AU - Vázquez, Olalla PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4904 AB - 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. PB - American Chemical Society T2 - ACS Central Science T1 - Bistable Photoswitch Allows in Vivo Control of Hematopoiesis VL - 8 IS - 1 SP - 57 EP - 66 DO - 10.1021/acscentsci.1c00434 ER -
@article{ author = "Albert, Lea and Nagpal, Jatin and Steinchen, Wieland and Zhang, Lei and Werel, Laura and Đoković, Nemanja and Ružić, Dušan and Hoffarth, Malte and Xu, Jing and Kaspareit, Johanna and Abendroth, Frank and Royant, Antoine and Bange, Gert and Nikolić, Katarina and Ryu, Soojin and Dou, Yali and Essen, Lars-Oliver and Vázquez, Olalla", year = "2022", 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.", publisher = "American Chemical Society", journal = "ACS Central Science", title = "Bistable Photoswitch Allows in Vivo Control of Hematopoiesis", volume = "8", number = "1", pages = "57-66", doi = "10.1021/acscentsci.1c00434" }
Albert, L., Nagpal, J., Steinchen, W., Zhang, L., Werel, L., Đoković, N., Ružić, D., Hoffarth, M., Xu, J., Kaspareit, J., Abendroth, F., Royant, A., Bange, G., Nikolić, K., Ryu, S., Dou, Y., Essen, L.,& Vázquez, O.. (2022). Bistable Photoswitch Allows in Vivo Control of Hematopoiesis. in ACS Central Science American Chemical Society., 8(1), 57-66. https://doi.org/10.1021/acscentsci.1c00434
Albert L, Nagpal J, Steinchen W, Zhang L, Werel L, Đoković N, Ružić D, Hoffarth M, Xu J, Kaspareit J, Abendroth F, Royant A, Bange G, Nikolić K, Ryu S, Dou Y, Essen L, Vázquez O. Bistable Photoswitch Allows in Vivo Control of Hematopoiesis. in ACS Central Science. 2022;8(1):57-66. doi:10.1021/acscentsci.1c00434 .
Albert, Lea, Nagpal, Jatin, Steinchen, Wieland, Zhang, Lei, Werel, Laura, Đoković, Nemanja, Ružić, Dušan, Hoffarth, Malte, Xu, Jing, Kaspareit, Johanna, Abendroth, Frank, Royant, Antoine, Bange, Gert, Nikolić, Katarina, Ryu, Soojin, Dou, Yali, Essen, Lars-Oliver, Vázquez, Olalla, "Bistable Photoswitch Allows in Vivo Control of Hematopoiesis" in ACS Central Science, 8, no. 1 (2022):57-66, https://doi.org/10.1021/acscentsci.1c00434 . .