Artificial Control of Cell Signaling Using a Photocleavable Cobalt(III)–Nitrosyl Complex

Sangwon Shin; Jisu Choe; Youngchan Park; Donghyun Jeong; Hyunjoon Song; Youngmin You; Daeha Seo; Jaeheung Cho

doi:10.1002/anie.201903106

Artificial Control of Cell Signaling Using a Photocleavable Cobalt(III)–Nitrosyl Complex

Sangwon Shin, Jisu Choe, Youngchan Park, Donghyun Jeong, Hyunjoon Song, Youngmin You, Daeha Seo, Jaeheung Cho

Department of Chemical and Biomolecular Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

Cells use gaseous molecules such as nitric oxide (NO) to transmit both intracellular and intercellular signals. In principle, the endogenous small molecules regulate physiological changes, but it is unclear how randomly diffusive molecules trigger and discriminate signaling programs. Herein, it is shown that gasotransmitters use time-dependent dynamics to discriminate the endogenous and exogenous inputs. For a real-time stimulation of cell signaling, we synthesized a photo-cleavable metal–nitrosyl complex, [Co^III(MDAP)(NO)(CH₃CN)]²⁺ (MDAP=N,N′-dimethyl-2,11-diaza[3,3](2,6)pyridinophane), which can stably deliver and selectively release NO with fine temporal resolution in the cytosol, and used this to study the extracellular signal-regulated kinases (ERKs), revealing how cells use both exogenous and endogenous NO to disentangle cellular responses. This technique can be to understand how diverse cellular signaling networks are dynamically interconnected and also to control drug delivery systems.

Original language	English
Pages (from-to)	10126-10131
Number of pages	6
Journal	Angewandte Chemie - International Edition
Volume	58
Issue number	30
DOIs	https://doi.org/10.1002/anie.201903106
Publication status	Published - 2019 Jul 22

Bibliographical note

Funding Information:
J.Ce., D.J., and J.C. were supported by the National Research Foundation (NRF) (2017R1A2B4005441 and 2018R1A5A1025511) and the Ministry of Science and ICT (MSIP) and Future Planning (CGRC 2016M3D3A01913243 and DGIST R&D Program 19-BD-0403) of South Korea. S.S., Y.P., and D.S. were supported by NRF funded by the MSIP (2017R1C1B2010945 and 2018R1A5A1025511). Y.Y. was supported by the MSIP through the GFP (Grant CISS-2012M3A6A6054204). Y.P. and H.S. were supported by NRF funded by the MSIP (2018R1A2B3004096).

Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

All Science Journal Classification (ASJC) codes

Catalysis
Chemistry(all)

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10.1002/anie.201903106

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title = "Artificial Control of Cell Signaling Using a Photocleavable Cobalt(III)–Nitrosyl Complex",

abstract = "Cells use gaseous molecules such as nitric oxide (NO) to transmit both intracellular and intercellular signals. In principle, the endogenous small molecules regulate physiological changes, but it is unclear how randomly diffusive molecules trigger and discriminate signaling programs. Herein, it is shown that gasotransmitters use time-dependent dynamics to discriminate the endogenous and exogenous inputs. For a real-time stimulation of cell signaling, we synthesized a photo-cleavable metal–nitrosyl complex, [CoIII(MDAP)(NO)(CH3CN)]2+ (MDAP=N,N′-dimethyl-2,11-diaza[3,3](2,6)pyridinophane), which can stably deliver and selectively release NO with fine temporal resolution in the cytosol, and used this to study the extracellular signal-regulated kinases (ERKs), revealing how cells use both exogenous and endogenous NO to disentangle cellular responses. This technique can be to understand how diverse cellular signaling networks are dynamically interconnected and also to control drug delivery systems.",

author = "Sangwon Shin and Jisu Choe and Youngchan Park and Donghyun Jeong and Hyunjoon Song and Youngmin You and Daeha Seo and Jaeheung Cho",

note = "Funding Information: J.Ce., D.J., and J.C. were supported by the National Research Foundation (NRF) (2017R1A2B4005441 and 2018R1A5A1025511) and the Ministry of Science and ICT (MSIP) and Future Planning (CGRC 2016M3D3A01913243 and DGIST R&D Program 19-BD-0403) of South Korea. S.S., Y.P., and D.S. were supported by NRF funded by the MSIP (2017R1C1B2010945 and 2018R1A5A1025511). Y.Y. was supported by the MSIP through the GFP (Grant CISS-2012M3A6A6054204). Y.P. and H.S. were supported by NRF funded by the MSIP (2018R1A2B3004096). Publisher Copyright: {\textcopyright} 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

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AU - Song, Hyunjoon

AU - You, Youngmin

AU - Seo, Daeha

AU - Cho, Jaeheung

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N2 - Cells use gaseous molecules such as nitric oxide (NO) to transmit both intracellular and intercellular signals. In principle, the endogenous small molecules regulate physiological changes, but it is unclear how randomly diffusive molecules trigger and discriminate signaling programs. Herein, it is shown that gasotransmitters use time-dependent dynamics to discriminate the endogenous and exogenous inputs. For a real-time stimulation of cell signaling, we synthesized a photo-cleavable metal–nitrosyl complex, [CoIII(MDAP)(NO)(CH3CN)]2+ (MDAP=N,N′-dimethyl-2,11-diaza[3,3](2,6)pyridinophane), which can stably deliver and selectively release NO with fine temporal resolution in the cytosol, and used this to study the extracellular signal-regulated kinases (ERKs), revealing how cells use both exogenous and endogenous NO to disentangle cellular responses. This technique can be to understand how diverse cellular signaling networks are dynamically interconnected and also to control drug delivery systems.

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Artificial Control of Cell Signaling Using a Photocleavable Cobalt(III)–Nitrosyl Complex

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