A5065231427- Pancreatic function and diabetes
- Chemical Synthesis and Analysis
- Nicotinic Acetylcholine Receptors Study
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Neuropeptides and Animal Physiology
- Diabetes Management and Research
- Click Chemistry and Applications
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Immune Cell Function and Interaction
- Ion channel regulation and function
- Molecular Biology Techniques and Applications
- Peptidase Inhibition and Analysis
- Biochemical and Structural Characterization
- T-cell and B-cell Immunology
- Diabetes Treatment and Management
- Adenosine and Purinergic Signaling
- Supramolecular Chemistry and Complexes
- Protein purification and stability
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Gene expression and cancer classification
- Hemoglobin structure and function
Stanford University
2020-2025
St George Hospital
2024-2025
UNSW Sydney
2024-2025
University of California, Irvine
2023
University of Utah
2015-2022
Texas A&M University
2022
Nagoya University
2022
Chinese University of Hong Kong
2022
University of Hong Kong
2022
Peking University
2022
Since its discovery and isolation, exogenous insulin has dramatically changed the outlook for patients with diabetes. However, even when strictly follow an regimen, serious complications can result as experience both hyperglycemic hypoglycemic states. Several chemically or genetically modified insulins have been developed that tune pharmacokinetics of activity personalized therapy. Here, we demonstrate a strategy chemical modification intended to promote long-lasting glucose-responsive...
A series of novel materials based on bi(9,9-diaryfluorene)s are the first examples pure aromatic hydrocarbons as potential UV emitters in organic light-emitting devices (OLEDs). The Figure, photographed a normal lighting environment, shows strong red, green, and blue emission from corresponding fluorescent dye solutions pumped by OLED this work, demonstrating OLED, its pumping capability.
A highly site-selective modification of peptides/proteins with aldehydes or carbohydrates under mild conditions was achieved.
Abstract We report the discovery of a peptide stapling and macrocyclization method using thiol–ene reactions between two cysteine residues an α,ω‐diene in high yields. This new approach enabled us to selectively modify native, unprotected peptides with variety modifications for helix stabilization or general macrocyclization. synthesized stapled Axin mimetic analogues demonstrated increased alpha helicity upon stapling. then p53 pure hydrocarbon linkers their abilities block p53‐MDM2...
The fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this insulin, Con-Ins G1, has unique characteristics relevant the design of new therapeutics. Here, we show snails provide rich source minimized ligands vertebrate receptor. Insulins from C. , tulipa and kinoshitai exhibit diverse sequences, yet all bind activate human Molecular dynamics reveal modes action are distinct any other insulins...
We developed a new cysteine-specific solubilizing tag strategy via cysteine-conjugated succinimide. This remains stable under common native chemical ligation conditions and can be efficiently removed with palladium-based catalysts. Utilizing this approach, we synthesized two proteins containing notably difficult peptide segments: interleukin-2 (IL-2) insulin. IL-2 synthesis represents the simplest most efficient approach to date, which is enabled by synthesize ligate long segments....
Abstract The application of thiol–yne/thiol–ene reactions to synthesize mono‐ and bicyclic‐stapled peptides proteins is reported. First, a thiol–ene‐based peptide‐stapling method in aqueous conditions was developed. This enabled the efficient stapling recombinantly expressed coil‐coiled proteins. resulting stapled protein demonstrated higher stability its secondary structure than unstapled version. Furthermore, thiol–yne coupling performed by using an α,ω‐diyne react with two cysteine...
Acute administration of deanol-p-acetamidobenzoate (Deaner; deanol) has been reported to elevate brain choline (CH) and acetylcholine (ACh) levels. We have developed a specific sensitive gas chromatographic assay measure deanol levels in tissue applied this our studies the effect acute on deanol, ACh Ch rodent brains. Details method are described text. This procedure is quantitative yields reproducible results over wide range concentrations (0.30-200 nmol). Seven endogenous pharmacological...
The synthesis of a stereochemically diverse library medium-sized rings accessible via 'build/couple/pair' strategy is described. Key aspects the include S(N)Ar cycloetherification linear amine template to afford eight stereoisomeric 8-membered lactams and subsequent solid-phase diversification these scaffolds yield 6488-membered library. Screening this compound collection in cell-based assay for suppression cytokine-induced beta-cell apoptosis resulted identification small-molecule...
Phenotypic cell-based screening is a powerful approach to small-molecule discovery, but major challenge of this strategy lies in determining the intracellular target and mechanism action (MoA) for validated hits. Here, we show that BRD0476, novel suppressor pancreatic β-cell apoptosis, inhibits interferon-gamma (IFN-γ)-induced Janus kinase 2 (JAK2) signal transducer activation transcription 1 (STAT1) signaling promote survival. However, unlike common JAK-STAT pathway inhibitors, BRD0476...
A novel four-disulfide insulin analog was designed with retained bioactivity and increased fibrillation stability.
In addition to degrading misfolded and damaged proteins, the proteasome regulates fate of cells in response stress. The role pro-inflammatory cytokine-induced human beta-cell apoptosis is unknown. Using INS-1, INS-1E islets exposed combinations IFNγ, IL-1β TNFα with or without small molecules, we assessed immunoproteasome pancreatic demise. Here, show that cytokines induce expression activity immuno-proteasome islets. Cytokine-induced subunits, but not activity, depended upon histone...
Insulin receptor (IR) activation requires coordinated engagement of two distinct insulin-binding sites, and recent structural insights have highlighted the role a disulfide bond in IR agonist S597 the...
Insulin – a hormone, medication, and protein is one of the most fascinating influential molecules ever discovered. Scientific understanding insulin ability to adapt it for medical needs cross boundaries knowledge, technology, research. For hundreds millions people living with diabetes around world, not only scientific achievement but an urgent necessity vital solution that saves lives every single day. The chemical functionalization has been desired various applications such as controlled...
Abstract Acute generalized exanthematous pustulosis We reviewed eight cases of acute managed in a tertiary hospital Singapore. Background (AGEP) is pustular reaction characterized by sudden eruption widespread nonfollicular sterile pustules associated with systemic symptoms. AGEP primarily believed to be an adverse drugs. Outside Europe, few reports exist on the clinical presentation AGEP. Methods A retrospective review patients who presented Singapore was performed. Results Eight were...
α9-Containing nicotinic acetylcholine receptors (nAChRs) are key targets for the treatment of neuropathic pain. α-Conotoxin RgIA4 is a peptide antagonist human α9α10 nAChRs with high selectivity. However, structural rearrangement reveals potential liability clinical applications. We herein report our designer RgIA analogues stabilized by methylene thioacetal as nonopioid analgesic agents. demonstrate that replacing disulfide loop I [CysI-CysIII] in skeleton results activity loss, whereas...
Aggregation represents a significant challenge for the long-term formulation stability of insulin therapeutics. The supramolecular PEGylation with conjugates cucurbit[7]uril and polyethylene glycol (CB[7]‒PEG) has been shown to stabilize formulations by reducing aggregation propensity. Yet prolonged in vivo duration action, arising from sustained complex formation subcutaneous depot, limits application scope meal-time uses could increase hypoglycemic risk several hours after meal....