A5005261579- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- NMR spectroscopy and applications
- Advanced NMR Techniques and Applications
- Crystallography and molecular interactions
- Advanced MRI Techniques and Applications
- Protein Structure and Dynamics
- Metabolism, Diabetes, and Cancer
- Ubiquitin and proteasome pathways
- Coordination Chemistry and Organometallics
- Asymmetric Synthesis and Catalysis
- Electron Spin Resonance Studies
- Bone health and osteoporosis research
- Monoclonal and Polyclonal Antibodies Research
- Photosynthetic Processes and Mechanisms
- Protein Degradation and Inhibitors
- Blood transfusion and management
- Platelet Disorders and Treatments
- Molecular spectroscopy and chirality
- Synthesis and pharmacology of benzodiazepine derivatives
- Estrogen and related hormone effects
- Bone Metabolism and Diseases
- Metabolism and Genetic Disorders
- Cellular Mechanics and Interactions
- Spectroscopy and Quantum Chemical Studies
Eli Lilly (United States)
2007-2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2024
Shandong University
2020
Indianapolis Zoo
2016-2019
Heilongjiang University of Science and Technology
2017
Harbin University of Science and Technology
2017
Lilly (China)
2016
Nanyang Technological University
2016
Lanzhou University
2012-2015
Taipei Veterans General Hospital
2008
Tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist, has, in clinical trials, demonstrated greater reductions glucose, body weight, and triglyceride levels compared with selective GLP-1R agonists people type 2 diabetes (T2D). However, cellular mechanisms by which GIPR agonism may contribute to these improved efficacy outcomes have not been fully defined. Using human adipocyte mouse models, we investigated how long-acting regulate...
3,4-dihydro-2H-1,2,4,3-triazaborol-3-yl-lithium 3 was synthesized and fully characterized. The 11B NMR spectrum, X-ray diffraction analysis, computational studies revealed the ionic nature of B–Li bond, indeed displays nucleophilic property which allowed preparation a series 1,2,4,3-triazaborol-3-yl-metal complexes (Al; 5, Au; 6, Zn; 7, Mg; 8, Sb; 9, Bi; 10). reacted with CO (1 atm) various isonitriles under ambient condition, mechanistic study suggests that reactions aryl proceed via an...
To evaluate its potential as a ligand discovery tool, we compare newly developed 1D protein-observed fluorine NMR (PrOF NMR) screening method with the well-characterized ligand-observed 1H CPMG screen. We selected first bromodomain of Brd4 model system to benchmark PrOF because high ligandability and need for small molecule inhibitors related epigenetic regulatory proteins. two methods' hit sensitivity, triaging ability, experiment speed, material consumption, false positives negatives. this...
Increasing the success rate and throughput of drug discovery will require efficiency improvements throughout process that is currently used in pharmaceutical community, including crucial step identifying hit compounds to act as drivers for subsequent optimization. Hit identification can be carried out through large compound collection screening often involves generation testing many hypotheses based on available knowledge. In practice, hypothesis involve selection promising chemical...
LY2090314 (3-[9-fluoro-2-(piperidin-1-ylcarbonyl)-1,2,3,4-tetrahydro[1,4]diazepino[6,7,1-hi]indol-7-yl]-4-imidazo[1,2-a]pyridin-3-yl-1H-pyrrole-2,5-dione) is an intravenous glycogen synthase kinase-3 inhibitor in oncology trials. Drug disposition was characterized after infusion of [<sup>14</sup>C]LY2090314 to rats and dogs, related available clinical data. exhibited high clearance (approximating hepatic blood flow) a moderate volume distribution (∼1–2 l/kg) resulting rapid elimination...
Fragment-based ligand discovery has been successful in targeting diverse proteins. Despite drug-like molecules having more 3D character, traditional fragment libraries are largely composed of flat, aromatic fragments. The use 3D-enriched fragments for enhancing library diversity is underexplored especially against protein-protein interactions. Here, we evaluate using bromodomains. Bromodomains highly ligandable, but selectivity remains challenging, particularly bromodomain and extraterminal...
The human insulin receptor signalling system plays a critical role in glucose homeostasis. Insulin binding brings about extensive conformational change the extracellular region that turn effects trans-activation of intracellular tyrosine kinase domains and downstream signalling. Of particular therapeutic interest is whether can be replicated by molecules other than insulin. Here, we present single-particle cryoEM structures show how 33-mer polypeptide unrelated to cross-link two sites on...
Caltractin (centrin) is a member of the calmodulin subfamily EF-hand Ca<sup>2+</sup>-binding proteins that an essential component microtubule-organizing centers in many organisms ranging from yeast and algae to humans. The protein contains two homologous domains linked by flexible tether; each domain capable binding Ca<sup>2+</sup> ions. In effort search for domain-specific functional properties caltractin, isolated were subcloned expressed <i>Escherichia coli</i>. affinities dependence...
Centrin is an EF-hand calcium-binding protein closely related to the prototypical calcium sensor calmodulin. It found in microtubule-organizing centers of organisms ranging from algae and yeast man. In vitro, C-terminal domain centrin binds centrosomal Kar1p a calcium-dependent manner, whereas N-terminal does not show any appreciable affinity for Kar1p. To obtain deeper insights into structural basis centrin's function, we have characterized affinities Chlamydomonas reinhardtii peptide...
Abstract We propose a family of doubly compensated multiplicity‐edited heteronuclear single quantum coherence (HSQC) pulse sequences. The key difference between our proposed sequences and the compensation refocusing inefficiency with synchronized inversion sweeps (CRISIS)‐HSQC experiments they are based on is that conventional rectangular 180° pulses proton channel in latter have been replaced by computer‐optimized broadband (BIPs) superior performance as well much improved tolerance to B 1...
Centrin is an essential component of microtubule-organizing centers in organisms ranging from algae and yeast to humans. It EF-hand calcium-binding protein with homology calmodulin but distinct calcium binding properties. In a previously proposed model, the C-terminal domain centrin serves as constitutive anchor target proteins, N-terminal sensor signals. The three-dimensional structure Chlamydomonas rheinhardtii has been determined presence by solution NMR spectroscopy. found occupy open...
The first asymmetric total syntheses of (+)-dihydrolyfoline and (−)-5-epi-dihydrolyfoline have been achieved in five six steps with 4.6% 14% overall yields, respectively, which the chiral biaryl axes were constructed a highly regioselective stereoselective manner via biogenetic enzymatic oxidative couplings phenols, requisite quinolizidinone cores prepared by an Mannich reaction.
Protein-observed <sup>19</sup>F (PrOF) NMR is an emerging tool for ligand discovery.
Acyl azetidines exhibit nonplanar hybridization, leading to lower amide-like character of the corresponding (O)C–N bonds. This impacts N-acryloyl by producing enhanced electrophilicy at appended Michael acceptors. Herein, reactivity data are reported in presence glutathione (GSH) phosphate buffer (pH 7.4) 37 °C. Wide ranges observed varying substitution acceptor or modulating electron-withdrawing substituents C3 position azetidine.
Mass balance and metabolism studies using radiolabeled substances are well recognized as an important part of the drug development process. In this study, we directly assessed use fluorine nuclear magnetic resonance (19F NMR) to achieve quantitative mass balance, metabolism, distribution information for fluorinated compounds, without need synthesis or study. As a test case, disposition pefloxacin, fluoroquinolone antibiotic, was evaluated in rats 19F NMR parallel with Urine, bile, feces...