Light-controlled inhibition of the circadian regulator RORγ DOI Creative Commons
Martin Reynders, Sabine Willems, Julian A. Marschner

et al.

Published: July 31, 2023

Retinoic acid receptor-related orphan receptor γ (RORγ) is a circadian regulator and has emerged as experimental therapeutic target in inflammation immunity. The cyclic temporal role of RORγ rhythms makes temporally-resolved pharmacological control this particularly intriguing. To achieve next-generation tools to study biology, we designed ligands featuring central azobenzene photoswitch, that act light-dependent inverse agonists. Structural optimization enabled efficient photocontrol over inhibition, with remarkable potency on excellent selectivity related receptors. These high-specificity photopharmaceuticals can serve high-precision the dynamic modulation signaling pathways inflammatory disorders.

Language: Английский

Synthesis and crystal structure of tetramethyl (E)-4,4′-(ethene-1,2-diyl)bis(5-nitrobenzene-1,2-dicarboxylate) DOI Creative Commons

Artjom Businski,

Thuy Chinh Ta,

Niklas Gindullis

et al.

Acta Crystallographica Section E Crystallographic Communications, Journal Year: 2024, Volume and Issue: 80(4), P. 435 - 438

Published: March 28, 2024

The title compound, C 22 H 18 N 2 O 12 , was obtained as a by-product during the planned synthesis of 1,2-bis(2-nitro-4,5-dimethyl phthalate)ethane by oxidative dimerization starting from dimethyl-4-methyl-5-nitro phthalate. To identify this compound unambiguously, single-crystal structure analysis performed. asymmetric unit consists half molecule that is located at centre inversion. As result symmetry restrictions, shows an E configuration around double bond. Both phenyl rings are coplanar, whereas nitro and two methyl ester groups rotated out ring plane 32.6 (1), 56.5 (2) 49.5 (2)°, respectively. In crystal, molecules connected into chains extending parallel to axis pairs C—H...O hydrogen bonds tri-periodic network additional hydrogen-bonding interactions.

Language: Английский

Citations

0
Cholesterol Decorated Diazocine Gelator with Photo‐ and Thermo‐Responsive Properties for Smart Window DOI
Yaxin Wang,

Yuan Yuan,

Shuaipeng Zhang

et al.

Chinese Journal of Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

Comprehensive Summary A new gelator ( BAzo‐Chol ) comprising a diazocine core and two cholesterol units linked via carbamate groups has been designed synthesized. Its gelation ability in several kinds of organic solvents is identified. Investigations with scanning electron microscopy (SEM), transmission (TEM), rheological measurements, UV ‐ vis absorption 1 H NMR spectroscopy reveal that can self‐assemble into elastically interpenetrating one‐dimensional nanostructures organogels through cooperative effect the π‐π interactions, hydrogen‐bonding, van der Waals forces. Moreover, unconventional Z / E conformational transitions these organogels, due to inclusion diazocine, endow gels excellent photo‐responsive gel‐sol transition remarkable visible light‐induced chromic properties. Lastly, its sensitive response light accompanied by distinct changes both colour transparency transitions, potential application current smart windows signified.

Language: Английский

Citations

0
A High‐Quality Photoswitchable Probe that Selectively and Potently Regulates the Transcription Factor RORγ DOI Creative Commons
Martin Reynders, Sabine Willems, Julian A. Marschner

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(49)

Published: Sept. 9, 2024

Abstract Der Retinsäure‐Rezeptor‐verwandte Waisen‐Rezeptor γ (RORγ) ist ein nuklearer Hormonrezeptor mit vielfältigen biologischen Funktionen in der Regulation zirkadianen Uhr, bei Entzündungen und Immunität. Seine zyklisch‐zeitliche Rolle Rhythmen seine zellspezifische Aktivität im Immunsystem machen ihn zu einer interessanten Zielstruktur für die räumlich zeitlich lokalisierte Pharmakologie. Um Werkzeuge entwickeln, denen RORγ‐Biologie angemessener räumlicher zeitlicher Auflösung untersucht werden kann, haben wir durch Einbau von Azobenzol‐Photoschaltern Liganden‐Konsensstrukturen lichtabhängige inverse RORγ‐Agonisten entwickelt. Strukturoptimierungen führten photoschaltbaren RORγ‐Inhibitoren, hohes Maß an Licht‐kontrollierter bemerkenswerter On‐Target‐Potenz hervorragender Selektivität gegenüber verwandten Rezeptoren kombinieren. Diese auf dem Gebiet Photopharmakologie seltene Qualität zeichnet sie als hochwertige photoschaltbare Sonden aus, nun hochpräzise zur Untersuchung räumlichen dynamischen Feinheiten RORγ‐Wirkung Signalübertragung entzündlichen Erkrankungen dienen können.

Citations

0
Synthesis and Photochromism of Diazocine Derivatives: Relationship Between Photoswitching Properties and Molecular Structures DOI
Yaxin Wang,

Yulan Chen

Chemical Research in Chinese Universities, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Language: Английский

Citations

0
Light-controlled inhibition of the circadian regulator RORγ DOI Creative Commons
Martin Reynders, Sabine Willems, Julian A. Marschner

et al.

Published: July 31, 2023

Retinoic acid receptor-related orphan receptor γ (RORγ) is a circadian regulator and has emerged as experimental therapeutic target in inflammation immunity. The cyclic temporal role of RORγ rhythms makes temporally-resolved pharmacological control this particularly intriguing. To achieve next-generation tools to study biology, we designed ligands featuring central azobenzene photoswitch, that act light-dependent inverse agonists. Structural optimization enabled efficient photocontrol over inhibition, with remarkable potency on excellent selectivity related receptors. These high-specificity photopharmaceuticals can serve high-precision the dynamic modulation signaling pathways inflammatory disorders.

Language: Английский

Citations

1