A5086708050- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis and Biological Evaluation
- Click Chemistry and Applications
- Crystallography and molecular interactions
- Ion channel regulation and function
- Chemical Synthesis and Analysis
- Radical Photochemical Reactions
- Microbial Natural Products and Biosynthesis
- Asymmetric Hydrogenation and Catalysis
- Protein Structure and Dynamics
- Analytical Chemistry and Chromatography
- Asymmetric Synthesis and Catalysis
- Organoboron and organosilicon chemistry
- Molecular Sensors and Ion Detection
- Catalytic C–H Functionalization Methods
- Cholinesterase and Neurodegenerative Diseases
- Catalytic Cross-Coupling Reactions
- Chemical synthesis and alkaloids
- Insect and Pesticide Research
- Photoreceptor and optogenetics research
University of Bristol
2016-2023
California Institute of Technology
2023
At Bristol
2018
Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method examine the cellular subcellular pharmacokinetic properties these compounds in living cells. Here, we developed new intensity-based drug-sensing fluorescent reporters (iDrugSnFRs) nicotinic dianicline, cytisine, two cytisine derivatives – 10-fluorocytisine...
Differentiating nicotinic acetylcholine receptors (nAChR) to target the high-affinity nicotine α4β2 subtype is a major challenge in developing effective addiction therapies. Although cytisine 1 and varenicline 2 (current smoking-cessation agents) are partial agonists of α4β2, these drugs display full agonism at α7 nAChR subtype. Site-specific modification (−)-cytisine via Ir-catalyzed C‒H activation provides access C(10) variants 6–10, 13, 14, 17, 20, 22, docking studies reveal that...
Nicotinic acetylcholine receptors (nAChRs) are crucial for communication between synapses in the central nervous system. As such, they also implicated several neuropsychiatric and addictive diseases. Cytisine is a partial agonist of some nAChRs has been used smoking cessation. Previous studies have established binding model agonists to nAChR subtypes. Here, we evaluate extent which this applies cytisine at α4β2 nAChR, subtype that known play prominent role nicotine addiction. Along with...
Nicotinic acetylcholine receptors (nAChRs) play an important role in neurotransmission and are also involved addiction several disease states. There is significant interest therapeutic targeting of nAChRs; however, achieving selectivity for one subtype over others has been a longstanding challenge, given the close structural similarities across family. Here, we characterize binding interactions α3β4 nAChR via structure–function studies involving noncanonical amino acid mutagenesis...
The ability to affect asymmetric reduction of heterocyclic β-aminoacrylates 1 (n = 1-3) has been assessed with pyrrolidine and piperidone variants generating the corresponding N-heterocyclic β(2)-amino acids 3b 5b high enantioselectivity (≥97% ee) using a Rh/WALPHOS catalyst combination. use carboxylic acid substrate was essential; esters do undergo but led racemic products. seven-ring azepanone variant (as 9b) underwent reduction, only minimal level induction observed.
Study of <i>α</i>6<i>β</i>4 nicotinic acetylcholine receptors (nAChRs) as a pharmacological target has recently gained interest because their involvement in analgesia, control catecholamine secretion, dopaminergic pathways, and aversive pathways. However, an extensive characterization the human nAChRs been vitiated by technical difficulties resulting poor receptor expression. In 2020, Knowland collaborators identified BARP (<i>β</i>-anchoring regulatory protein), previously known...
Cytisine undergoes ready fragmentation to provide a highly flexible (and “privileged”) piperidine scaffold capable of exploring diversity chemical space.
The high regioselectivity associated with the iridium-catalysed borylation of pyridones has been exploited to provide a very direct and efficient entry C(10) doubly substituted CC4 variants cytisine. Two approaches have evaluated based on (i) C–H activation cytisine (or an N-substituted derivative) followed by N-alkylation (to enable dimer formation) (ii) itself. Both access C(10)-functionalized derivatives, but allows for wider range functional group interconversions be tolerated.
Cytisine, a natural product with high affinity for clinically relevant nicotinic acetylcholine receptors (nAChRs), is used as smoking-cessation agent. The compound displays an excellent clinical profile and hence there interest in derivatives that may be further improved or find use the treatment of other conditions. Here, binding cytisine derivative modified by addition 3-(hydroxypropyl) moiety (ligand 4 ) to Aplysia californica acetylcholine-binding protein ( Ac AChBP), surrogate nAChR...
ABSTRACT Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method examine the cellular subcellular pharmacokinetic properties these compounds in living cells. Here, we developed new intensity-based drug sensing fluorescent reporters (“iDrugSnFRs”) nicotinic dianicline, cytisine, two cytisine derivatives –...
(S)-(−)-Cotinine 2 undergoes direct and site-selective iridium-catalyzed borylation to provide boronate ester 3 bromide 4 which offer flexible entry a range of C(5)-substituted cotinine variants.