A5065779473- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Influenza Virus Research Studies
- Glycosylation and Glycoproteins Research
- Synthesis and Catalytic Reactions
- Chemical Synthesis and Reactions
- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Fluorine in Organic Chemistry
- Sulfur-Based Synthesis Techniques
- Synthesis and Biological Evaluation
- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- Quinazolinone synthesis and applications
- Diet, Metabolism, and Disease
- Crystallization and Solubility Studies
- Respiratory viral infections research
- Synthesis of Tetrazole Derivatives
- X-ray Diffraction in Crystallography
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Cancer-related gene regulation
- Radical Photochemical Reactions
- Genetics, Aging, and Longevity in Model Organisms
Institute of Chemistry, Academia Sinica
2016-2024
Academia Sinica
2008-2024
National Taiwan University
2002-2023
National Defense Medical Center
2020
National Science and Technology Council
2019
Genomics Research Center, Academia Sinica
2005-2014
Scripps Research Institute
2005-2007
Institute of Biological Chemistry, Academia Sinica
2005-2006
Tamkang University
1998
The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 deaths worldwide as November 2020. Currently, there are no effective antivirals approved the Food Drug Administration to contain this pandemic except antiviral agent remdesivir. In addition, trimeric spike protein on viral surface is highly glycosylated almost 200,000 variants with mutations at 1,000 positions its 1,273 amino acid sequence were reported, posing a major challenge...
Using d-xylose as an appropriate chiral precursor, we have synthesized active neuraminidase inhibitor oseltamivir, antiflu drug Tamiflu, and novel phosphonate congeners that exhibit even stronger activities by inhibiting the neuraminidases of wild-type H274Y mutant H1N1 H5N1 viruses. Molecular modeling neuraminidase−phosphonate complex indicates a pertinent binding mode with three arginine residues in site. Discovery such potent inhibitors will offer opportunity to development new...
We have designed a low fluorescent azido-BODIPY-based probe AzBOCEt (Az10) that undergoes copper(I)-catalyzed 1,3-dipolar cycloadditions with alkynes to yield strongly triazole derivatives. The quantum of product T10 is enhanced by 52-fold as compared upon excitation at wavelength above 500 nm. Quantum mechanical calculations indicate the increase in fluorescence formation due lowering HOMO energy level aryl moiety reduce process acceptor photoinduced electron transfer. shown label...
A variety of aldehydes reacted with iodine in ammonia water at room temperature to give the nitrile intermediates, which were trapped by addition hydrogen peroxide, sodium azide, or dicyandiamide produce their corresponding amides, tetrazoles, and 1,3,5-triazines modest high yields. The one-pot tandem reactions conducted media, products obtained simply extraction filtration.
A series of primary alcohols and aldehydes were treated with iodine in ammonia water under microwave irradiation to give the intermediate nitriles, which without isolation underwent [2 + 3] cycloadditions dicyandiamide sodium azide afford high yields corresponding triazines tetrazoles, including α-amino- dipeptidyl tetrazoles optical purity.
Tamiflu and the highly potent neuraminidase inhibitor tamiphosphor have been synthesized in 11 steps greater than 20 % overall yields from an haloarene (1S,2S)-cis-diol. The key transformations include a regio- stereoselective bromoamidation, palladium-catalyzed carbonylation or phosphonylation reaction (see scheme; tamiflu: A=CO2Et, B=NH3+H2PO4−, tamiphosphor: A=PO(ONH4)2, B=NH2).
Two phosphonate compounds 1a (4-amino-1-phosphono-DANA) and 1b (phosphono-zanamivir) are synthesized shown more potent than zanamivir against the neuraminidases of avian human influenza viruses, including oseltamivir-resistant strains. For first time, practical synthesis these is realized by conversion sialic acid to peracetylated phosphono-DANA diethyl ester (5) as a key intermediate in three steps novel approach. In comparison with zanamivir, high affinity can be partly attributable strong...
Significance Glycosylation is considered to be a major posttranslational modification, and O -GlcNAcylation known affect protein folding function. In this study, we show that the methyltransferase EZH2, which catalyzes methylation of histone 3 at lysine 27 form H3K27m3, requires enhance its stability enzymatic activity promote tumor progression. We further in N-terminal region EZH2 stabilizes enzyme S729 catalytic domain essential for di- trimethylation. This study indicates selective...
The carnivorous mushroom
A diversified library of peptide anilides was prepared, and their inhibition activities against the SARS-CoV 3CL protease were examined by a fluorogenic tetradecapeptide substrate. The most potent inhibitor is an anilide derived from 2-chloro-4-nitroaniline, l-phenylalanine 4-(dimethylamino)benzoic acid. This competitive with Ki = 0.03 μM. molecular docking experiment indicates that P1 residue this distant nucleophilic SH Cys145 in active site.
Five active metal-conjugated inhibitors (PMA, TDT, EPDTC, JMF1586 and JMF1600) bound with the 3C-like protease of severe acute respiratory syndrome (SARS)-associated coronavirus were analyzed crystallographically. The complex structures reveal two major inhibition modes: Hg(2+)-PMA is coordinated to C(44), M(49) Y(54) a square planar geometry at S3 pocket, whereas each Zn(2+) four zinc-inhibitors tetrahedrally H(41)-C(145) catalytic dyad. For anti-SARS drug design, this Zn(2+)-centered...
Three methods are utilized to synthesize a variety of 6,8-di-C-glycosylflavones bearing identical or distinct glycosyl moieties. Some C-glycosylation compounds found have better anti-inflammation activities than the parent flavones. Among them, 6,8-di-C-glucosylapigenin (known as vicenin-2) shows inhibition TNF-α expression and NO production with IC50 values 6.8 5.2 μM, respectively.
Oseltamivir phosphonic acid (tamiphosphor, 3a), its monoethyl ester (3c), guanidino-tamiphosphor (4a), and (4c) are potent inhibitors of influenza neuraminidases. They inhibit the replication viruses, including oseltamivir-resistant H275Y strain, at low nanomolar to picomolar levels, significantly protect mice from infection with lethal doses viruses when orally administered 1 mg/kg or higher doses. These compounds stable in simulated gastric fluid, liver microsomes, human blood largely free...
Abstract Background Colorectal cancer (CRC) is a worldwide with rising annual incidence. New medications for patients CRC are still needed. Recently, fluorescent chemical probes have been developed imaging and therapy. Signal transducer activator of transcription 1 (STAT1) has complex functions in tumorigenesis its role needs further investigation. Methods RNA sequencing datasets the NCBI GEO repository were analyzed to investigate expression STAT1 CRC. Xenograft mouse models, tail vein...
Significance Multiple fungal lineages have independently evolved carnivorous behaviors, preying on a diversity of nematodes as an adaptation for survival in low-nutrient environments. The edible oyster mushroom Pleurotus ostreatus is known to paralyze nematode prey, but the mechanism was unclear. We show that P. triggers massive calcium influx and rapid cell necrosis neuromuscular system C. elegans via nematode’s sensory cilia—a mode action conserved across nematodes. Our study reveals...
With use of iodine as an appropriate oxidant, unprotected and unmodified aldoses undergo oxidative amidation with a variety functionalized amines, α-amino esters, peptides, whereas KDO, sialic acid, other α-keto acids proceed decarboxylation followed by in situ amidation. Glycoside bond many functional groups are inert under such mild reaction conditions. This protocol for direct ligation carbohydrate molecules looks promising the development general efficient synthesis glycoconjugates.