A5040268097- Photochromic and Fluorescence Chemistry
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Click Chemistry and Applications
- Photoreceptor and optogenetics research
- Multiple Myeloma Research and Treatments
- Photonic and Optical Devices
- Retinoids in leukemia and cellular processes
- bioluminescence and chemiluminescence research
- Chemical Synthesis and Analysis
- Advanced biosensing and bioanalysis techniques
- Retinal Development and Disorders
- Energetic Materials and Combustion
- Neuroblastoma Research and Treatments
- Chemical Reactions and Mechanisms
- Nanoplatforms for cancer theranostics
- Receptor Mechanisms and Signaling
- Advanced Fluorescence Microscopy Techniques
- Advancements in Semiconductor Devices and Circuit Design
- Aluminum toxicity and tolerance in plants and animals
- Cancer Mechanisms and Therapy
- Acute Myeloid Leukemia Research
- Melanoma and MAPK Pathways
Ludwig-Maximilians-Universität München
2013-2024
New York University
2019-2023
Center for Integrated Protein Science Munich
2019
KU Leuven
2017
We present a modular approach to control the small molecule–mediated degradation of cellular proteins interest using light.
Azobenzenes are versatile photoswitches that have found widespread use in a variety of fields, ranging from photopharmacology to the material sciences. In addition regular azobenzenes, cyclic diazocines recently emerged. Although fascinating conformational and photophysical properties, their has been limited by synthetic accessibility. Herein, we present general, high-yielding protocol relies on oxidative cyclization dianilines. combination with modular substrate synthesis, it allows for...
Covalent kinase inhibitors account for some of the most successful drugs that have recently entered clinic and many others are in preclinical development. A common strategy is to target cysteines vicinity ATP binding site using an acrylamide electrophile. To increase tissue selectivity inhibitors, it could be advantageous control reactivity these electrophiles with light. Here, we introduce covalent JNK3 function as photoswitchable affinity labels (PALs). Our lead compounds contain a...
Azobenzene molecular switches are widely used to photocontrol material properties, and biological activity in cell culture, via photoisomerisation between E Z isomers. However, because population photoswitching is incomplete, their dynamic range of property control often small; they cannot be operated with red/NIR light, usually not applicable deep tissue. Here, we demonstrate a general method for efficient single-photon azobenzenes, glutamate receptor activity, at >700 nm live We use...
Here we develop a high-performance approach to photoswitching, by exploiting singlet manifold photoredox between azobenzenes and covalently attached auxiliary chromophores. This enables well-penetrating red/NIR light of 630-740 nm, which usually do not respond, perform Z→E photoisomerisation that is also 100% complete highly photon-efficient. Crucially, this process biocompatible, tolerates molecular oxygen, photostable, it avoids the drawbacks triplet photochemistry; substituent patterns...
Abstract The fluorine‐containing polynitro energetic molecule (2‐fluoro‐2,2‐dinitroethyl)‐2,2,2‐trinitroethylnitramine and the corresponding precursors were synthesized investigated as potential high‐energy dense oxidizers. compounds have been characterized by using various analytical methods, single‐crystal X‐ray diffraction, vibrational spectroscopy (IR Raman), multinuclear NMR spectroscopy, elemental analysis, mass spectrometry, differential scanning calorimetry (DSC) measurements....
Abstract Various energetic polynitro esters, carbamates, and nitrocarbamates that were derived from the amino acid glycine fully characterized by single‐crystal X‐ray diffraction, vibrational spectroscopy (IR Raman), multinuclear NMR spectroscopy, elemental analysis, differential scanning calorimetry (DSC). Owing to their positive oxygen balance, suitability of these compounds as potential oxidizers in formulations was investigated discussed. In addition, heats formation products calculated...
Abstract The lipid composition of cellular membranes is dynamic and undergoes remodelling affecting biophysical properties, such as membrane fluidity, which are critical to biological function. Here, we introduce an optical approach manipulate fluidity based on exogenous synthetic fatty acid with azobenzene photoswitch, termed FAAzo4 . Cells rapidly incorporate into phosphatidylcholine (PC), the major phospholipid in mammalian cells, a concentration- cell type-dependent manner. This...
Abstract Retinoic acid receptor‐related orphan receptor γ (RORγ) is a nuclear hormone with multiple biological functions in circadian clock regulation, inflammation, and immunity. Its cyclic temporal role rhythms, cell‐specific activity the immune system, make it an intriguing target for spatially temporally localised pharmacology. To create tools that can study RORγ biology appropriate spatiotemporal resolution, we designed light‐dependent inverse agonists by building azobenzene...
Hundreds of proteins determine the function synapses, and synapses define neuronal circuits that subserve myriad brain, cognitive, behavioral functions. It is thus necessary to precisely manipulate specific at sub-cellular locations times elucidate roles particular in brain function. We developed PHOtochemically TArgeting Chimeras (PHOTACs) as a strategy optically degrade with high spatial temporal precision. PHOTACs are small molecules that, upon wavelength-selective illumination, catalyze...
Here, we performed photo-SAR studies in a series of photoswitchable tubulin inhibiting antimitotics, and discovered that fluorescent antenna motifs permit their single-photon photoisomerisation biological conditions at up to >600 nm; were also able visualise the temporal onset long-term photopharmacological effects, using large-field-of-view microscopy. Previously, azobenzene analogues polymerisation inhibitor combretastatin A4 (PSTs) had been developed optically control microtubule...
PROTACs (proteolysis targeting chimeras) are bifunctional molecules that tag proteins for ubiquitylation by an E3 ligase complex and subsequent degradation the proteasome. They have emerged as powerful tools to control levels of specific cellular on verge being clinically used. We now introduce photoswitchable can be activated with temporal spatial precision light provides. These trifunctional molecules, which we named PHOTACs, consist a ligand ligase, photoswitch, protein interest....
PROTACs (proteolysis targeting chimeras) are bifunctional molecules that tag proteins for ubiquitylation by an E3 ligase complex and subsequent degradation the proteasome. They have emerged as powerful tools to control levels of specific cellular on verge being clinically used. We now introduce photoswitchable can be activated with temporal spatial precision light provides. These trifunctional molecules, which we named PHOTACs, consist a ligand ligase, photoswitch, protein interest....
<p><i>PROTACs (proteolysis targeting chimeras) are bifunctional molecules that tag proteins for ubiquitylation by an E3 ligase complex and subsequent degradation the proteasome. They have emerged as powerful tools to control levels of specific cellular on verge being clinically used. We now introduce photoswitchable PROTACs can be activated with temporal spatial precision light provides. These trifunctional molecules, which we named PHOTACs, consist a ligand ligase, photoswitch,...
Abstract Immunomodulatory drugs (IMiDs), which include thalidomide and its derivatives, have emerged as the standard of care against multiple myeloma. They function molecular glues that bind to E3 ligase cereblon (CRBN) induce protein interactions with neosubstrates, including transcription factors Ikaros (IKZF1) Aiolos (IKZF3). The subsequent ubiquitylation degradation these underlies antiproliferative activity IMiDs. Here, we introduce photoswitchable immunomodulatory (PHOIMiDs) can be...
Abstract Covalent kinase inhibitors account for some of the most successful drugs that have recently entered clinic and many others are in preclinical development. A common strategy is to target cysteines vicinity ATP binding site using an acrylamide electrophile. To increase tissue selectivity inhibitors, it could be advantageous control reactivity these electrophiles with light. Here, we introduce covalent JNK3 function as photoswitchable affinity labels (PALs). Our lead compounds contain...
We develop reagents to optically control microtubule dynamics, with (1) lensless microscopy track their bioactivity; (2) photo-SAR find GFP-compatible reagents; & (3) fluorophore antennas drive single-photon isomerisation even ≥600 nm.
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...
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...
AIDS virus antibody in polytransfused dialysis patients vaccinated against hepatitis BPatients receiving long term haemodialysis are at increased risk of B infection.Given the similar transmission routes and acquired immune deficiency syndrome (AIDS) it is surprising that no seroprevalence data on infection with lymphadenopathy associated virus/human T cell lymphotropic type III (LAV/HTLV-III) centres have been published.We present from 18 Belgium, where we surveyed all who had received...