A5102727462- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Neurotransmitter Receptor Influence on Behavior
- Psychedelics and Drug Studies
- Chemical synthesis and alkaloids
- Enzyme Catalysis and Immobilization
- Biological and pharmacological studies of plants
- Phytochemistry and Biological Activities
- Microbial Natural Products and Biosynthesis
- Cancer Mechanisms and Therapy
- Forensic Toxicology and Drug Analysis
- Conducting polymers and applications
- Quinazolinone synthesis and applications
- Nicotinic Acetylcholine Receptors Study
- Electrochemical sensors and biosensors
- Melanoma and MAPK Pathways
- Biochemical and Molecular Research
- Pharmacogenetics and Drug Metabolism
- Electrochemical Analysis and Applications
- Diet, Metabolism, and Disease
- Retinoids in leukemia and cellular processes
- Macrophage Migration Inhibitory Factor
- Sesquiterpenes and Asteraceae Studies
- Transgenic Plants and Applications
- Synthesis and Biological Evaluation
Hangzhou Normal University
2019-2024
University of Kentucky
2010-2023
Scripps Research Institute
2018-2019
University of Chinese Academy of Sciences
2010
Chinese Academy of Sciences
2008
San Francisco VA Medical Center
1991
Cocaine is a widely abused drug without U.S. Food and Drug Administration-approved medication. There recognized, promising anticocaine medication to accelerate cocaine metabolism, producing biologically inactive metabolites via route similar the primary cocaine-metabolizing pathway [i.e., hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma]. An ideal, therapeutically valuable mutant of human BChE should have not only significantly improved catalytic activity against (−)-cocaine...
Cocaine abuse is a world-wide public health and social problem without US Food Drug Administration-approved medication. An ideal anticocaine medication would accelerate cocaine metabolism, producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Our recent studies have led to the discovery desirable, highly hydrolases (CocHs) that can efficiently detoxify inactivate affecting normal functions CNS. Preclinical clinical data demonstrated...
Affordable and physiologically relevant three-dimensional (3D) cell-based assays used in high-throughput screening (HTS) are on the rise early drug discovery. These technologies have been aided by recent adaptation of novel microplate treatments spheroid culturing techniques. One such technology involves use nanoparticle (NanoShuttle-PL) labeled cells custom magnetic drives to assist cell aggregation ensure rapid 3D structure formation after dispensed into microtiter plates. Transitioning...
The present study was aimed to explore the correlation between protein structure and catalytic efficiency of butyrylcholinesterase (BChE) mutants against (−)-cocaine by modeling rate-determining transition state (TS1), i.e., for first step chemical reaction process, hydrolysis catalyzed various human BChE in comparison with wild type. Molecular TS1 structures revealed that mutations on certain nonactive site residues can indirectly affect enzyme through enhancing or weakening overall...
It has been known that cocaine produces its toxic and physiological effects through not only itself, but also norcocaine formed from oxidation catalysed by microsomal CYP (cytochrome P450) 3A4 in the human liver. The catalytic parameters (kcat Km) of BChE (butyrylcholinesterase) three mutants (i.e. A199S/S287G/A328W/Y332G, A199S/F227A/S287G/A328W/E441D A199S/F227A/S287G/A328W/Y332G) for have characterized present study first time compared with those cocaine. On basis obtained kinetic data,...
Gene transfer of a human cocaine hydrolase (hCocH) derived from butyrylcholinesterase (BChE) by 5 mutations (A199S/F227A/S287G/A328W/Y332G) has shown promise in animal studies for treatment addiction. To predict the physiological fate and immunogenicity this enzyme humans, comparable was created tested conspecific host. Thus, similar (A199S/S227A/S287G/A328W/Y332G) were introduced into mouse BChE to obtain CocH (mCocH). The cDNA incorporated viral vectors based on: a) serotype-5...
Cocaine is a widely abused drug without an FDA (Food and Drug Administration)-approved medication. It has been recognized that ideal anti-cocaine medication would accelerate cocaine metabolism producing biologically inactive metabolites via route similar to the primary cocaine-metabolizing pathway, i.e. human BChE (butyrylcholinesterase)-catalysed hydrolysis. However, native low catalytic activity against cocaine. We recently designed discovered mutant (A199S/F227A/S287G/A328W/Y332G) with...
Cocaine is one of the most addictive drugs, and there still no FDA (Food Drug Administration)-approved medication specific for cocaine abuse. A promising therapeutic strategy to accelerate metabolism, producing biologically inactive metabolites via a route similar primary cocaine-metabolizing pathway, i.e. hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma. However, native BChE has low catalytic efficiency against abused cocaine, (−)-cocaine. Our recently designed discovered...
It is known that the majority of cocaine users also consume alcohol. Alcohol can react with to produce a significantly more cytotoxic compound, cocaethylene. Hence truly valuable cocaine-metabolizing enzyme as treatment for abuse/overdose should be efficient not only itself, but The catalytic parameters (kcat and KM) human BChE (butyrylcholinesterase) two mutants (known hydrolases E14-3 E12-7) cocaethylene are characterized in present study, first time, comparison those cocaine. On basis...
This manuscript follows a single patient with pancreatic adenocarcinoma for five year period, detailing the clinical record, pathology, dynamic evolution of molecular and cellular alterations as well responses to treatments chemotherapies, targeted therapies immunotherapies. DNA RNA samples from biopsies blood identified set changes in allelic imbalances copy number variations response therapies. Organoid cultures established over time were employed extensive drug testing determine if this...
A novel 6/6/5/6 tetracyclic polyketide named chartspiroton (1) was isolated from a medicinal plant endophytic Streptomyces in Dendrobium officinale. The complete structure assignment with absolute stereochemistry elucidated through spectroscopic data, computational calculations, and single-crystal X-ray diffraction. Chartspiroton features an unprecedented naphthoquinone derivative spiro-fused benzofuran lactone moiety. plausible biosynthetic pathway for 1 suggested intriguing oxidative...
Twelve guaianolide-type sesquiterpene oligomers with diverse structures were isolated from the whole plants of Ainsliaea fragrans, including a novel trimer (1) and two new dimers (2, 3). The chemical compounds elucidated through spectroscopic data interpretation computational calculations. Ainsfragolide is an unusual guaianolide generated C-C linkage at C2'-C15″, which may be biosynthesized prospectively further Michael addition. Cytotoxicity results showed that ainsfragolide was most potent...
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with an elusive etiology. Aberrant activation of c-Jun N-terminal kinase 1 (JNK1) has been implicated in its pathogenesis. Through combination structure-based drug design structure-activity relationship (SAR) optimization, series pyrimidine-2,4-diamine scaffold derivatives have developed as potent JNK1 inhibitors. Compound
The poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing polymer scaffolds holds promise precisely constructing complex tissue architecture, however resultant usually lack sufficient bioactivity to effectively generate new tissue.Herein, printing-based strategy via cryo-printing technology was employed fabricate customized polyurethane (PU) porous that mimic native meniscus. In order enhance scaffold for...
Three new polyketide dimers named huoshanmycins A‒C (1-3) were isolated from a plant endophytic Streptomyces sp. HS-3-L-1 in the leaf of Dendrobium huoshanense, which was collected Cultivation base Jiuxianzun Huoshanshihu Co., Ltd. The dimeric structures composed unusual polyketides SEK43, SEK15, or UWM4, with unique methylene linkage. Their elucidated through comprehensive 1D-/2D-NMR and HRESIMS spectroscopic data analysis. cytotoxicity against MV4-11 human leukemia cell by Cell Counting...
Endophyte has now become a potential source for the discovery of novel natural products, as they participate in biochemical pathways their hosts and produce analogous or bioactive compounds. As an epiphytic plant, Dendrobium officinale is one precious Chinese medicines with various activities. It well known containing diverse endophytes, but so far not much about secondary metabolites.the plant tissues were cut cultured on agar plates to isolate purify endophytic bacteria from officinale....
Mouse butyrylcholinesterase (mBChE) and an mBChE-based cocaine hydrolase (mCocH, i.e. the A¹⁹⁹S/S²²⁷A/S²⁸⁷G/A³²⁸W/Y³³²G mutant) have been characterized for their catalytic activities against cocaine, naturally occurring (-)-cocaine, in comparison with corresponding human BChE (hBChE) hBChE-based (hCocH, A¹⁹⁹S/F²²⁷A/S²⁸⁷G/A³²⁸W/Y³³²G mutant). It has demonstrated that mCocH hCocH improved efficiency of mBChE hBChE (-)-cocaine by ~8- ~2000-fold respectively, although efficiencies other...