A5041499508- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- Respiratory viral infections research
- Heat shock proteins research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Skin and Cellular Biology Research
- Immune Cell Function and Interaction
- Fungal and yeast genetics research
- Polysaccharides and Plant Cell Walls
- Microbial Natural Products and Biosynthesis
- SARS-CoV-2 and COVID-19 Research
- Bacterial Genetics and Biotechnology
- Biochemical and Molecular Research
- Immunotherapy and Immune Responses
- Cancer therapeutics and mechanisms
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Immune Response and Inflammation
- Biochemical and Structural Characterization
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Metabolism, Diabetes, and Cancer
Genomics Research Center, Academia Sinica
2016-2025
Academia Sinica
2008-2022
National Taiwan University
2010-2020
National Taiwan University Hospital
2020
Institute of Biomedical Sciences, Academia Sinica
2020
National Cheng Kung University
2011-2016
General Atomics (United States)
2015
Sirenas (United States)
2015
Genomics (United Kingdom)
2009-2013
National Tsing Hua University
1993-2010
Recent cases of avian influenza H5N1 and the swine-origin 2009 H1N1 have caused a great concern that global disaster like 1918 pandemic may occur again. Viral transmission begins with critical interaction between hemagglutinin (HA) glycoprotein, which is on viral coat influenza, sialic acid (SA) containing glycans, are host cell surface. To elucidate role HA glycosylation in this important interaction, various defined glycoforms were prepared, their binding affinity specificity studied by...
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...
A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is develop a broadly protective vaccine that elicits long-term immunity. As key immunogen, viral surface spike (S) protein frequently mutated, and conserved epitopes are shielded glycans. Here, we revealed S glycosylation has site-differential effects on infectivity. We found generated lung epithelial cells glycoforms associated with increased Compared fully glycosylated protein,...
H5N1 influenza viruses have spread extensively among wild birds and domestic poultry. Cross-species transmission of these to humans has been documented in over 380 cases, with a mortality rate approximately 60%. There is great concern that virus would acquire the ability efficiently between humans, thereby becoming pandemic threat. An vaccine must, therefore, be an integral part any preparedness plan. However, traditional methods making vaccines yet produce candidate could induce potently...
Globo H (GH) is a hexasaccharide specifically overexpressed on variety of cancer cells and therefore, good candidate for vaccine development. To identify the optimal carrier adjuvant combination, we chemically synthesized linked GH to protein, including keyhole limpet hemocyanion, diphtheria toxoid cross-reactive material (CRM) 197 (DT), tetanus toxoid, BSA, combined with an adjuvant, it was administered mice study immune response. Glycan microarray analysis antiserum obtained indicated that...
Amyotrophic lateral sclerosis (ALS) associated with TAR DNA-binding protein 43 (TDP-43) aggregation has been considered as a lethal and progressive motor neuron disease. Recent studies have shown that both C-terminal TDP-43 (C-TDP-43) aggregates oligomers were neurotoxic pathologic agents in ALS frontotemporal lobar degeneration (FTLD). However, misfolding long an undruggable target by applying conventional inhibitors, agonists, or antagonists. To provide this unmet medical need, we aim to...
As influenza viruses have developed resistance towards current drugs, new inhibitors that prevent viral replication through different inhibitory mechanisms are useful. In this study, we a screening procedure to search for antiinfluenza from 1,200,000 compounds and identified previously reported as well compounds. Several were the RNA-dependent RNA polymerase (RdRP), including nucleozin its analogs. The most potent analog, 3061 (FA-2), inhibited of A/WSN/33 (H1N1) virus in MDCK cells at...
A library of 27 sialosides, including seventeen 2,3-linked and ten 2,6-linked glycans, has been prepared to construct a glycan array used profile the binding specificity different influenza hemagglutinins (HA) subtypes, especially from 2009 swine-originated H1N1 seasonal viruses. It was found that HAs Brisbane strain share similar profiles yet affinities toward various α2,6 sialosides. Analysis HA subtypes indicate minimum set 5 oligosaccharides can be differentiate H1, H3, H5, H7, H9...
We have reported that treatment with CdCl2 at 40–100 μm induces the heat shock proteins (HSPs) in 9L rat brain tumor cells, during which activation of factor (HSF) is essentially involved. By exploiting protein kinase inhibitors, we further analyzed possible participation specific kinases above processes. It was found induction HSP70 cells treated a high concentration cadmium (i.e. 100 μm) preceded by phosphorylation and p38 mitogen-activated (p38MAPK), while low (60 accompanied...
Bacterial transpeptidase and transglycosylase on the surface are essential for cell wall synthesis, many antibiotics have been developed to target transpeptidase; however, problem of antibiotic resistance has arisen caused a major threat in bacterial infection. The considered be another excellent target, but no this enzyme. Here, we determined crystal structure Staphylococcus aureus membrane-bound transglycosylase, monofunctional glycosyltransferase, complex with lipid II analog 2.3 Å...
Sweetening the deal: N. meningitidis serogroup W135 capsular oligosaccharides were synthesized in lengths from disaccharides to decasaccharides. Sera mice immunized with these oligosaccharide–protein conjugates examined by a glycan microarray (see picture) and bactericidal assay for antibody specificity ability kill bacteria. As service our authors readers, this journal provides supporting information supplied authors. Such materials are peer reviewed may be re-organized online delivery, but...
Globo H-based therapeutic cancer vaccines have been tested in clinical trials for the treatment of late stage breast, ovarian, and prostate cancers. In this study, we explored H analogue antigens with an attempt to enhance antigenic properties vaccine design. The analogues modification at reducing or nonreducing end were synthesized using chemoenzymatic methods, these modified then conjugated carrier protein diphtheria toxoid cross-reactive material (CRM) 197 (DT), combined a glycolipid C34...
Abstract A metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ZnO-NP (60 ppm) and ClO 2 (42.5 in aqueous solution was prepared characterized by spectroscopy, transmission electron microscopy, dynamic light scattering analysis potentiometric titration. Based on the vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus (SARS-CoV-2) with effective concentration within range to be used as food additives. shown...
Moenomycin inhibits bacterial growth by blocking the transglycosylase activity of class A penicillin-binding proteins (PBPs), which are key enzymes in cell wall synthesis. We compared binding affinities moenomycin with various truncated PBPs using surface plasmon resonance analysis and found that transmembrane domain is important for binding. Full-length from 16 species were produced, their activities showed a correlation antimicrobial against Enterococcus faecalis Staphylococcus aureus . On...
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.
We have successfully developed a [1+2+3] one-pot strategy to synthesize the RM2 antigen hexasaccharide that was proposed be prostate tumor antigen. The structure of synthetic product verified by NMR analysis and antibody binding assay using glycan microarray. In addition, conjugated mutated diphtheria toxin (DT, CRM197) with different copy numbers adjuvant combinations form vaccine candidates. After vaccination in mice, we used microarrays monitor their immune response, results indicated...
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 The emergence of antibiotic resistance has prompted active research in the development antibiotics with new modes action. Among all essential bacterial proteins, transglycosylase polymerizes lipid II into peptidoglycan and is one most favorable targets because its vital role synthesis. Described this study a practical enzymatic method for synthesis II, coupled cofactor regeneration, to give product 50–70 % yield. This depends on two key steps: overexpression MraY I use undecaprenol...
Peramivir is a potent neuraminidase (NA) inhibitor for treatment of influenza infection by intravenous administration. By replacing the carboxylate group in peramivir with phosphonate group, phosphono-peramivir (6a), dehydration and deoxy derivatives (7a 8a) as well their corresponding monoalkyl esters are prepared from pivotal intermediate epoxide 12. Among these compounds, derivative 7a that has relatively rigid cyclopentene core structure exhibits strongest inhibitory activity (IC50 =...
Hemagglutinin (HA) is the immunodominant protein of influenza virus. We previously showed that mice injected with a monoglycosylated A HA (HA mg ) produced cross-strain-reactive antibodies and were better protected than fully glycosylated fg during lethal dose challenge. employed single B-cell screening platform to isolate cross-protective monoclonal antibody (mAb) 651 from immunized A/Brisbane/59/2007 (H1N1) virus (Bris/07). The mAb recognized head domain broad spectrum HAs groups 1 2...