A5054607938- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Photoreceptor and optogenetics research
- Photochromic and Fluorescence Chemistry
- Receptor Mechanisms and Signaling
- Marine Toxins and Detection Methods
- Oxidative Organic Chemistry Reactions
- Synthetic Organic Chemistry Methods
- Crystallography and molecular interactions
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Microbial Natural Products and Biosynthesis
- Spectroscopy and Quantum Chemical Studies
- Chemical synthesis and alkaloids
- Radical Photochemical Reactions
- Neuroscience of respiration and sleep
- Sulfur-Based Synthesis Techniques
- Synthesis and Catalytic Reactions
- Neuroscience and Neuropharmacology Research
- Carbohydrate Chemistry and Synthesis
- Organoboron and organosilicon chemistry
- CAR-T cell therapy research
- Asymmetric Synthesis and Catalysis
- Advanced Chemical Physics Studies
- Neuroendocrine regulation and behavior
New York University
2018-2025
VIR Biotechnology (United States)
2024
Ludwig-Maximilians-Universität München
2019
Serotonin receptors play central roles in neuromodulation and are critical drug targets for psychiatric disorders. Optical control of serotonin receptor subtypes has the potential to greatly enhance our understanding spatiotemporal dynamics function. While other neuromodulatory have been successfully rendered photoswitchable, reversible photocontrol not achieved, representing a major gap GPCR photopharmacology. Herein, we develop first tools that allow such control. Azo5HT-2 shows...
G protein-coupled receptors (GPCRs) are the most common targets of drug discovery. However, similarity between related GPCRs combined with complex spatiotemporal dynamics receptor activation in vivo has hindered development. Photopharmacology offers possibility using light to control location and timing action by incorporating a photoisomerizable azobenzene into GPCR ligand, enabling rapid reversible switching an inactive active configuration. Recent advances this area include (i)...
Tetrodotoxin (TTX) is a neurotoxic natural product that an indispensable probe in neuroscience, biosynthetic and ecological enigma, celebrated target of synthetic chemistry. Here, we present stereoselective synthesis TTX proceeds 22 steps from glucose derivative. The central cyclohexane ring its α-tertiary amine moiety were established by the intramolecular 1,3-dipolar cycloaddition nitrile oxide, followed alkynyl addition to resultant isoxazoline. A ruthenium-catalyzed hydroxylactonization...
α-Galactosylceramides are glycosphingolipids that show promise in cancer immunotherapy. After presentation by CD1d, they activate natural killer T cells (NKT), which results the production of a variety pro-inflammatory and immunomodulatory cytokines. Herein, we report synthesis biological evaluation photochromic derivatives KRN-7000, activity can be modulated with light. Based on established structure–activity relationships, designed photoswitchable analogues this glycolipid control...
Allylboron reagents are popular in synthesis owing to their versatility and the predictable stereochemical outcomes of reactions with carbonyl compounds. Herein, we describe (Z,Z)-hexadienyl bis-boronate 1, a configurationally stable, crystalline, easy handle compound, which represents class bis-allylic boron heretofore untapped synthetic potential. In combination chiral phosphoric acid catalyst, reagent can be employed for enantioselective allyl transfer reaction variety one-pot...
In the aftermath of COVID-19 pandemic, opportunities to modulate biological pathways common lifecycles viruses need be carefully considered.
Oxytocin is a neuropeptide critical for maternal physiology and social behavior, thought to be dysregulated in several neuropsychiatric disorders. Despite the biological neurocognitive importance of oxytocin signaling, methods are lacking activate receptors with high spatiotemporal precision brain peripheral mammalian tissues. Here we developed validated caged analogs which functionally inert until cage release triggered by ultraviolet light. We examined how focal versus global application...
Dopamine D2-like receptors (D2R, D3R, and D4R) control diverse physiological behavioral functions are important targets for the treatment of a variety neuropsychiatric disorders. Their complex distribution activation kinetics in brain make it difficult to target specific receptor populations with sufficient precision. We describe new toolkit light-activatable, fast-relaxing, covalently taggable chemical photoswitches that fully activate, partially or block receptors. This technology combines...
Abstract Serotonin receptors play central roles in neuromodulation and are critical drug targets for psychiatric disorders. Optical control of serotonin receptor subtypes has the potential to greatly enhance our understanding spatiotemporal dynamics function. While other neuromodulatory have been successfully rendered photoswitchable, reversible photocontrol not achieved, representing a major gap GPCR photopharmacology. Herein, we develop first tools that allow such control. Azo5HT‐2 shows...
Abstract Oxytocin is a neuropeptide critical for maternal physiology and social behavior, thought to be dysregulated in several neuropsychiatric disorders. Despite the biological neurocognitive importance of oxytocin signaling, methods are lacking activate receptors with high spatiotemporal precision brain peripheral mammalian tissues. Here we developed validated caged analogs which functionally inert until cage release triggered by ultraviolet light. We examined how focal versus global...
Abstract Allylische Bor‐Verbindungen haben vielseitige Anwendungsmöglichkeiten und zeichnen sich durch eine gute stereochemische Vorhersagbarkeit in der Reaktion mit Carbonylgruppen aus. Hier beschreiben wir die Synthese von ( Z , )‐Hexadienylbisboronat 1 das konfigurationsstabil, kristallin einfach zu handhaben ist. Es ist Teil einer Klasse bis‐allylischer Bor‐Reagenzien bislang nicht ausgeschöpftem Synthesepotential. Durch Katalyse chiralen Phosphorsäuren kann Reagenz enantioselektiven...
The serotonin receptor family of G protein-coupled receptors (GPCRs) and ligand-gated ion channels play central roles in neuromodulation are critical drug targets for the treatment psychiatric disorders. Optical control subtypes has potential to greatly enhance our understanding spatiotemporal dynamics function both at cellular level within neural circuits. While other neuromodulatory have been successfully rendered photoswitchable, reversible photocontrol not achieved, representing a major...
Two-dimensional electronic spectroscopy (2D ES) probes the energies of chromophores and their coupling, therefore technique is now widely used for studying excitation energy-transfer mechanisms. The ubiquity importance ofFörster Resonance Energy Transfer (FRET) demand a thorough study its signatures in 2D ES. Here, using principles from noisy-light to account spontaneous transfer event, we describe model that explicitly includes intramolecular vibrational modes necessary activate FRET. Our...
The serotonin receptor family of G protein-coupled receptors (GPCRs) and ligand-gated ion channels play central roles in neuromodulation are critical drug targets for the treatment psychiatric disorders. Optical control subtypes has potential to greatly enhance our understanding spatiotemporal dynamics function both at cellular level within neural circuits. While other neuromodulatory have been successfully rendered photoswitchable, reversible photocontrol not achieved, representing a major...
Tetrodotoxin (TTX) is an indispensable probe in neuroscience, a biosynthetic and ecological enigma, one of the most celebrated targets synthetic chemistry. Here, we present stereoselective synthesis TTX that proceeds 22 steps starting from readily available glucose derivative. The central cyclohexane ring its α-tertiary amine moiety was established via intramolecular 1,3-dipolar cycloaddition nitrile oxide, followed by alkynyl addition to resultant isoxazoline. After some carefully chosen...
Tetrodotoxin (TTX) is an indispensable probe in neuroscience, a biosynthetic and ecological enigma, one of the most celebrated targets synthetic chemistry. Here, we present stereoselective synthesis TTX that proceeds 22 steps starting from readily available glucose derivative. The central cyclohexane ring its α-tertiary amine moiety was established via intramolecular 1,3-dipolar cycloaddition nitrile oxide, followed by alkynyl addition to resultant isoxazoline. After some carefully chosen...