139 results on '"Xin, Shan"'
Search Results
2. Analysis of the Differences in Muscle Nutrition among Individuals of Different Sexes in Redclaw Crayfish, Cherax quadricarinatus
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Yuyan Sun, Xin Shan, Desheng Li, Xuxiao Liu, Zongao Han, Junjie Qin, Bin Guan, Leilei Tan, Jianbo Zheng, Min Wei, and Yongyi Jia
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amino acids ,muscle ,Endocrinology, Diabetes and Metabolism ,fat ,Molecular Biology ,Biochemistry ,fatty acids - Abstract
Redclaw crayfish (Cherax quadricarinatus) was introduced to China many years ago. In recent years, a breeding boom for C. quadricarinatus has been set off in China due to a breakthrough in key technology of seedling breeding. The size and growth rate of C. quadricarinatus vary greatly between female and male individuals, usually the size and growth rate of male individuals are bigger than that of female individuals. There is usually a certain linkage relationship between the sex traits of crustaceans and their own nutrition. In order to explore the linkage relationship between the sex traits of C. quadricarinatus and its nutritional components, this study measured and analyzed the muscle nutritional components of female and male individuals. The results showed that the meat yield rate of male individuals was significantly higher than that of females (p < 0.05), and the crude fat content was significantly lower than that for females (p < 0.05). The ratios of essential amino acids to total amino acids for females and males were 39.61% and 38.49%, respectively. The ratios of essential amino acids to non-essential amino acids were 79.69% and 75.66%, respectively, which far exceed FAO/WHO standards and both belong to high-quality protein. The total amount of flavor amino acids of male individuals was significantly higher than that of female individuals (p < 0.05). The total amount of polyunsaturated fatty acids and the polyunsaturated fatty acid eicosapentaenoic acid of males are both significantly higher than that of females (p < 0.05). Studies have shown that there are certain differences in nutrition between male and female individuals. Compared with female individuals, the meat yield rate, crude protein content, and edible value of the muscles of male individuals is higher.
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- 2023
- Full Text
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3. Additive-controlled synthesis of 1- and 2-deoxysugars from thioglycosides
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Xia Wu, Biao Wu, Chen-Fei Gao, Xin-Shan Ye, and De-Cai Xiong
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Organic Chemistry ,Biochemistry - Published
- 2021
4. Nattokinase Activity Guided Natto Fermentation Process Optimization
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Xiaojie Ren, Chao Huang, Xin Shan, Heng Ban, Baoyue Liu, Yu Du, Yuanda Song, and Xinhe Zhao
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Biochemistry ,Biotechnology - Published
- 2021
5. Synthesis and immunological evaluation of N-acyl modified Globo H derivatives as anticancer vaccine candidates
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Chengcheng Song, Xiu-Jing Zheng, Xin-Shan Ye, and Canjia Zhai
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Synthetic vaccine ,Glycosylation ,Glycoconjugate ,medicine.medical_treatment ,Pharmaceutical Science ,H antigen ,010402 general chemistry ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Immune system ,Drug Discovery ,medicine ,Pharmacology ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Immunogenicity ,Organic Chemistry ,0104 chemical sciences ,chemistry ,Cancer research ,biology.protein ,Molecular Medicine ,Antibody ,Adjuvant - Abstract
Globo H is a tumor-associated carbohydrate antigen (TACA), which serves as a valuable target for antitumor vaccine or cancer immunotherapies. However, most TACAs are T-cell-independent, and they cannot induce powerful immune response due to their poor immunogenicity. To address this problem, herein, several Globo H analogues with modification on the N-acyl group were prepared through a preactivation-based glycosylation strategy from the non-reducing end to the reducing end. These modified Globo H derivatives were then conjugated with carrier protein CRM197 to form glycoconjugates as anticancer vaccine candidates, which were used in combination with adjuvant glycolipid C34 for immunological studies. The immunological effects of these synthetic vaccine candidates were evaluated on Balb/c mice. The results showed that the fluorine-modified N-acyl Globo H conjugates can induce higher titers of IgG antibodies that can recognize the naturally occurring Globo H antigen on the surface of cancer cells and can eliminate cancer cells in the presence of a complement, indicating the potential of these synthetic glycoconjugates as anticancer vaccine candidates.
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- 2021
6. One-step synthesis of multi-colored ZnO nanoparticles for white light-emitting diodes
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Rui Zhou, Xue-Ying Wu, Qi Zhao, Kai-Kai Liu, Lin Dong, and Chong-Xin Shan
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Biophysics ,General Chemistry ,Condensed Matter Physics ,Biochemistry ,Atomic and Molecular Physics, and Optics - Published
- 2022
7. Recent advances in glycan synthesis
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Xin-Shan Ye and Bo-Han Li
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0301 basic medicine ,Glycan ,Glycosylation ,biology ,Chemistry ,Stereoisomerism ,Chemistry Techniques, Synthetic ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Chemical synthesis ,Enzymes ,0104 chemical sciences ,Analytical Chemistry ,carbohydrates (lipids) ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Polysaccharides ,biology.protein - Abstract
Carbohydrates play important roles in life science, but their synthesis is always hampered by their complicated chemical structures. Scientists have never stopped trying to solve the problem of glycan synthesis from various aspects. Here a brief overview of recent progress in glycan synthesis, including chemical approaches, chemoenzymatic approaches, and automated synthesis, will be discussed, focusing on the efficiency of new glycosylation methods, the stereoselectivity of coupled products, and their applications in the assembly of complex glycan chains.
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- 2020
8. Design, Synthesis, and Structure–Activity Relationships of Indoline-Based Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-Like 2 (Keap1-Nrf2) Protein–Protein Interaction Inhibitors
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Tian Liu, Jing Zhao, Han Zhang, Lv-Bin Hu, Qidong You, Xue Li, Wen-Xin Shan, Yan Wang, Zheng-Yu Jiang, and Hai-Shan Zhou
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Cardiotonic Agents ,Indoles ,NF-E2-Related Factor 2 ,Oxidative phosphorylation ,Plasma protein binding ,01 natural sciences ,Protein–protein interaction ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Downregulation and upregulation ,Drug Discovery ,Humans ,Structure–activity relationship ,030304 developmental biology ,0303 health sciences ,Kelch-Like ECH-Associated Protein 1 ,KEAP1 ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Biochemistry ,chemistry ,Drug Design ,Indoline ,Thermodynamics ,Molecular Medicine ,Protein Binding - Abstract
The Keap1 (Kelch-like ECH-associated protein 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)-ARE (antioxidant response element) pathway is the major defending mechanism against oxidative stresses, and directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has been an attractive strategy to target oxidative stress-related diseases, including cardiovascular diseases. Here, we describe the design, synthesis, and structure-activity relationships (SARs) of indoline-based compounds as potent Keap1-Nrf2 PPI inhibitors. Comprehensive SAR analysis and thermodynamics-guided optimization identified 19a as the most potent inhibitor in this series, with an IC50 of 22 nM in a competitive fluorescence polarization assay. Further evaluation indicated the proper drug-like properties of 19a. Compound 19a dose-dependently upregulated genes and protein level of Nrf2 as well as its downstream markers and showed protective effects against lipopolysaccharide-induced injury in both H9c2 cardiac cells and mouse models. Collectively, we reported here a novel indoline-based Keap1-Nrf2 PPI inhibitor as a potential cardioprotective agent.
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- 2020
9. Rapid and Prolonged Antidepressant-like Effect of Crocin Is Associated with GHSR-Mediated Hippocampal Plasticity-related Proteins in Mice Exposed to Prenatal Stress
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Dong Xiao, Ruyan Wu, Weiwei Tao, Yu Dong, and Xin Shan
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Physiology ,Offspring ,Cognitive Neuroscience ,Growth hormone secretagogue receptor ,Hippocampal formation ,Pharmacology ,Hippocampus ,Biochemistry ,Crocin ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Animals ,Medicine ,Receptors, Ghrelin ,Adverse effect ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,Mice, Inbred BALB C ,0303 health sciences ,Neuronal Plasticity ,business.industry ,digestive, oral, and skin physiology ,Cell Biology ,General Medicine ,Carotenoids ,Antidepressive Agents ,chemistry ,Prenatal stress ,Antidepressant ,Female ,business ,Stress, Psychological ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Prenatal stress (PNS) has a prolonged and adverse effect on offspring, leading to a significantly increased vulnerability to developing depression in their later life. Traditional therapies have delayed onset and limited efficacy; thus, it remains an urgent need to find novel medications with fast-onset and high-efficacy potentials. Crocin, with its structure clearly examined, has shown antidepressant-like effects. However, few studies extensively investigated its effect especially in mice exposed to PNS. Using an established PNS model, we tested whether crocin could have a rapid and persistent antidepressant-like effect in PNS mice. Growth hormone secretagogue receptor (GHSR) and phosphoinositide 3-kinase (PI3K) inhibitors were used to test their effects in antidepressant-like effect of crocin. Hippocampal GHSR-PI3K signaling was examined both in PNS mice treated with a single dose of crocin and in combination of GHSR inhibitor. PNS mice showed depression-like behaviors at juvenile and adulthood, and crocin induced an instant and persistent antidepressant-like response in PNS mice in a dose-dependent manner. Moreover, crocin increased the expression of hippocampal synaptic plasticity-associated proteins through the restoration of GHSR-PI3K signaling. Inhibitions of both GHSR and PI3K abolished the effect of crocin in alleviating depressive-like behaviors. More importantly, GHSR inhibitor JMV2959 blocked the enhanced expression of hippocampal plasticity-related proteins induced by crocin. The present study demonstrated that crocin induced a fast-onset and prolonged antidepressant effect in PNS mice and suggested that GHSR-PI3K signaling may play a key role in crocin's effect at least partially by a restoration of hippocampal synaptic plasticity-associated proteins.
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- 2020
10. Design, synthesis and evaluation of carbamate-containing sialyltransferase inhibitors
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Wenming Li, Wanjun Yan, De-Cai Xiong, and Xin-Shan Ye
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Carbamate ,biology ,Biochemistry ,Design synthesis ,Chemistry ,Sialyltransferase ,medicine.medical_treatment ,medicine ,biology.protein ,Pharmaceutical Science - Published
- 2020
11. Engineering a bacterial sialyltransferase for di-sialylation of a therapeutic antibody
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Yue Wang, Xin-Shan Ye, Liangren Zhang, Mingqun Wang, Kaimeng Liu, Zhenming Liu, and Xiaodong Dou
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chemistry.chemical_classification ,Glycosylation ,biology ,Photobacterium ,Sialyltransferase ,Organic Chemistry ,Mutant ,Mutagenesis (molecular biology technique) ,Protein Engineering ,Biochemistry ,Antibodies ,Sialyltransferases ,carbohydrates (lipids) ,chemistry.chemical_compound ,Enzyme ,chemistry ,Sialic Acids ,biology.protein ,Physical and Theoretical Chemistry ,Antibody ,Bioorthogonal chemistry ,Glycoprotein ,beta-D-Galactoside alpha 2-6-Sialyltransferase - Abstract
Terminal α-2,6-sialylation of N-glycans is a humanized glycosylation that affects the properties and efficacy of therapeutic glycoproteins. Fc di-sialylation (a biantennary N-glycan with two α-2,6-linked sialic acids) of IgG antibodies imparts them with enhanced anti-inflammatory activity and other roles. However, the microheterogeneity of N-glycoforms presents a challenge for therapeutic development. Therefore, controlled sialylation has drawn considerable attention, but direct access to well-defined di-sialylated antibodies remains limited. Herein, a one-pot three-enzyme protocol was developed by engineering a bacterial sialyltransferase to facilitate the modification of therapeutic antibodies with N-acetylneuraminic acid or its derivatives towards optimized glycosylation. To overcome the low proficiency of bacterial sialyltransferase in antibody remodeling, the Photobacterium sp. JT-ISH-224 α-2,6-sialyltransferase (Psp2,6ST) was genetically engineered by terminal truncation and site-directed mutagenesis based on its protein crystal structure. With the optimized reaction conditions and using activity-based screening of various Psp2,6ST variants, a truncated mutant Psp2,6ST (111-511)-His6 A235M/A366G was shown to effectively improve the catalytic efficiency of antibody di-sialylation. Herceptin and the donor substrate promiscuity allow the introduction of bioorthogonal modifications of N-acetylneuraminic acid into antibodies for site-specific conjugation. 2-AB hydrophilic interaction chromatography analysis of the released N-glycans and intact mass characterization confirmed the high di-sialylation of Herceptin via the optimized one-pot three-enzyme reaction. This study established a versatile enzymatic approach for producing highly di-sialylated IgG antibodies. It provides new insights into engineering bacterial sialyltransferase for adaptation to the enzymatic glycoengineering of therapeutic antibodies and the glycosite-specific conjugation of antibodies.
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- 2020
12. C-Glycosylation enabled by N-(glycosyloxy)acetamides
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Xia Wu, De-Cai Xiong, Bo-Han Li, Meng Liu, Miao Liu, Tian Li, and Xin-Shan Ye
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Reaction conditions ,chemistry.chemical_classification ,Glycosylation ,Silylation ,Aryl ,Organic Chemistry ,Biochemistry ,Enol ,carbohydrates (lipids) ,chemistry.chemical_compound ,chemistry ,Organic chemistry ,lipids (amino acids, peptides, and proteins) ,Glycosyl ,Phenols ,Physical and Theoretical Chemistry ,Alkyl - Abstract
The C-glycosylation of C-nucleophiles including allyltrimethylsilane, silyl enol ethers and phenols with N-(glycosyloxy)acetamides as glycosyl donors has been realized. This protocol provides a convenient and practical route for the synthesis of alkyl C-glycosides and aryl 2-deoxy-β-C-glycosides under mild reaction conditions.
- Published
- 2020
13. Glycan Assembly Strategy: From Concept to Application
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Xianjin Qin, Mingli Liu, and Xin-Shan Ye
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Glycan ,Glycosylation ,biology ,Carbohydrate chemistry ,Chemistry ,General Chemical Engineering ,Carbohydrate synthesis ,General Chemistry ,Computational biology ,Biochemistry ,carbohydrates (lipids) ,chemistry.chemical_compound ,Hot topics ,Polysaccharides ,Materials Chemistry ,Natural source ,biology.protein - Abstract
Glycans have been hot topics in recent years due to their exhibition of numerous biological activities. However, the heterogeneity of their natural source and the complexity of their chemical synthesis impede the progress in their biological research. Thus, the development of glycan assembly strategies to acquire plenty of structurally well-defined glycans is an important issue in carbohydrate chemistry. In this review, the latest advances in glycan assembly strategies from concepts to their applications in carbohydrate synthesis, including chemical and enzymatic/chemo-enzymatic approaches, as well as solution-phase and solid-phase/tag-assisted synthesis, are summarized. Furthermore, the automated glycan assembly techniques are also outlined.
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- 2021
14. Synthesis and biological evaluation of bergenin derivatives as new immunosuppressants
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Youhong Niu, Qin Li, Meng Wang, Xin-Shan Ye, Yan-Fen Wu, Chengcheng Song, and Lihua Deng
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Pharmacology ,biology ,Organic Chemistry ,Pharmaceutical Science ,Bergenin ,Alkylation ,biology.organism_classification ,Biochemistry ,Combinatorial chemistry ,chemistry.chemical_compound ,Chemistry ,chemistry ,Drug Discovery ,Splenocyte ,Molecular Medicine ,Bergenia ,Inhibitory effect ,IC50 ,Biological evaluation - Abstract
Bergenin, which is isolated from Bergenia species, exhibits various pharmacological properties. In the search for new types of immunosuppressants, a series of bergenin derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The experimental data demonstrated that compounds 7 and 13 showed the strongest inhibition effects on mouse splenocyte proliferation (IC(50) = 3.52 and 5.39 μM, respectively). Further studies revealed that the inhibitory effect may come from the suppression of both IFN-γ and IL-4 cytokines. Alkylated derivatives of bergenin with n-hexyl and n-heptyl on the two phenolic hydroxyl groups showed better inhibitory activities. The hydrophobicity of bergenin derivatives, the configuration of the 4-OH in bergenin, and the ability to form hydrogen bonds of the substituents on the C-4 position are important to the immunosuppressive activity. This work proved that the modifications of bergenin may represent a new route to the discovery of a new class of immunosuppressive agents.
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- 2021
15. Low CP Overhead Waveform Design for Multi-Path Channels with Timing Synchronization Error
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Jing Chen, Baobing Wang, Jianzhong Guo, Xin Shan, and Dejin Kong
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OFDM ,symbol repetition ,multi-path channel ,timing synchronization error ,cyclic prefix ,Electrical and Electronic Engineering ,Biochemistry ,Instrumentation ,Atomic and Molecular Physics, and Optics ,Analytical Chemistry - Abstract
In classical orthogonal frequency division multiplexing (OFDM) systems, inserting the cyclic prefix (CP) is necessary before each symbol to overcome the multi-path effect, which, however, occupies numerous time-frequency radio resources, resulting in hampered spectrum efficiency. To address this issue, in this paper, symbol repetition aware OFDM (SR-OFDM) is developed to lower the overhead of CP. In the proposed SR-OFDM, multiple symbols share the same CP with which we examine that the multi-path channels can also be overcome by a simple single-tap equalization without causing any interference. Moreover, after the discrete Fourier transform at the receiver, different symbols are proved to be separated in the time domain, which is beneficial for lowering the demodulation complexity. Furthermore, it is revealed that the above conclusions still hold even under timing synchronization errors, which makes the proposed SR-OFDM favorable in real systems. Extensive simulations validate the efficacy of our proposed SR-OFDM system under the multi-path channels with or without timing synchronization errors.
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- 2022
16. O-GlcNAcylation increases PYGL activity by promoting phosphorylation
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Yan-Fang Chen, Jing-Jing Zhu, Jing Li, and Xin-Shan Ye
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Glucose ,Neoplasms ,Humans ,Phosphorylation ,N-Acetylglucosaminyltransferases ,Biochemistry ,Protein Processing, Post-Translational ,Glycogen ,Acetylglucosamine - Abstract
O-GlcNAcylation is a post-translational modification that links metabolism with signal transduction. High O-GlcNAcylation appears to be a general characteristic of cancer cells. It promotes the invasion, metastasis, proliferation and survival of tumor cells, and alters many metabolic pathways. Glycogen metabolism increases in a wide variety of tumors, suggesting that it is an important aspect of cancer pathophysiology. Herein we focused on the O-GlcNAcylation of liver glycogen phosphorylase (PYGL)—an important catabolism enzyme in the glycogen metabolism pathway. PYGL expressed in both HEK 293T and HCT116 was modified by O-GlcNAc. And both PYGL O-GlcNAcylation and phosphorylation of Ser15 (pSer15) were decreased under glucose and insulin, whereas increased under glucagon and Na2S2O4 (hypoxia) conditions. Then, we identified the major O-GlcNAcylation site to be Ser430, and demonstrated that pSer15 and Ser430 O-GlcNAcylation were mutually reinforced. Lastly, we found that Ser430 O-GlcNAcylation was fundamental for PYGL activity. Thus, O-GlcNAcylation of PYGL positively regulated pSer15 and therefore its enzymatic activity. Our results provided another molecular insight into the intricate post-translational regulation network of PYGL.
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- 2021
17. Sensing of mycobacterial arabinogalactan by galectin‐9 exacerbates mycobacterial infection
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Shaorong Gao, Anca Dorhoi, Gang Pei, Haipeng Liu, Yong Wu, Jie Wang, Yang Wang, Zhonghua Liu, Bo Yan, Baoxue Ge, Feifei Li, Ruiliang Jin, Xiangyang Wu, Ruijuan Zheng, Lin Wang, Fen Tang, Peng Zhang, Chang Chen, Xin-Shan Ye, Stefan H. E. Kaufmann, Xiaochen Huang, Wei Sha, Lingming Chen, Lu Zhang, Hua Yang, Jiayu Chen, Detian Lai, Fei Wang, Peng Wang, Pedro Moura-Alves, Felix Randow, Mingtong Ma, Yajuan Cao, Lianhua Qin, Jianxia Chen, Jinyu Zhang, Liang-Dong Lyu, Gucheng Zeng, and Qin Sun
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Galectins ,galectin‐9 ,virulence factor ,Galactans ,Biochemistry ,Article ,Virulence factor ,Microbiology ,Mycobacterium tuberculosis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Arabinogalactan ,Genetics ,Animals ,Molecular Biology ,Zebrafish ,030304 developmental biology ,Galectin ,0303 health sciences ,Mycobacterium bovis ,mycobacterial arabinogalactan ,biology ,Kinase ,Chemistry ,matrix metalloproteinases ,transforming growth factor β‐activated kinase 1 ,Articles ,biology.organism_classification ,Microbiology, Virology & Host Pathogen Interaction ,030217 neurology & neurosurgery ,Signal Transduction ,Transforming growth factor ,Mycobacterium - Abstract
Mycobacterial arabinogalactan (AG) is an essential cell wall component of mycobacteria and a frequent structural and bio‐synthetical target for anti‐tuberculosis (TB) drug development. Here, we report that mycobacterial AG is recognized by galectin‐9 and exacerbates mycobacterial infection. Administration of AG‐specific aptamers inhibits cellular infiltration caused by Mycobacterium tuberculosis (Mtb) or Mycobacterium bovis BCG, and moderately increases survival of Mtb‐infected mice or Mycobacterium marinum‐infected zebrafish. AG interacts with carbohydrate recognition domain (CRD) 2 of galectin‐9 with high affinity, and galectin‐9 associates with transforming growth factor β‐activated kinase 1 (TAK1) via CRD2 to trigger subsequent activation of extracellular signal‐regulated kinase (ERK) as well as induction of the expression of matrix metalloproteinases (MMPs). Moreover, deletion of galectin‐9 or inhibition of MMPs blocks AG‐induced pathological impairments in the lung, and the AG‐galectin‐9 axis aggravates the process of Mtb infection in mice. These results demonstrate that AG is an important virulence factor of mycobacteria and galectin‐9 is a novel receptor for Mtb and other mycobacteria, paving the way for the development of novel effective TB immune modulators., Arabinogalactan is a virulence factor of mycobacteria. Binding of galectin‐9 to mycobacterial arabinogalactan triggers matrix metalloproteinases via TAK1‐ERK signaling, which promotes mycobacterial infection and increases lung injury.
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- 2021
18. Forecasting Guangdong’s Marine Science and Technology, Marine Economy, and Employed Persons by Coastal Regions—Based on Rolling Grey MGM(1,m) Model
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Xin Shan and Yun Cao
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marine economy ,marine science and technology ,GM(1,1) mode ,RMGM(1,m) model ,Geography, Planning and Development ,Aquatic Science ,Biochemistry ,Water Science and Technology - Abstract
The development of marine scientific and technological innovation is an important force for realizing the high-quality development of the marine economy. The purpose of this paper is to predict the development trend of marine science and technology development, marine economy, and employed persons by coastal regions in Guangdong Province, and to give policy suggestions for the future direction of the development of marine technology in Guangdong. Considering the new information priority principle, this paper uses the data from 2011 to 2016 to predict the development trend of marine science and technology, marine economy, and employed persons by coastal regions in Guangdong Province from 2017 to 2022 with the rolling RMGM(1,m) model. It is found that the level of marine science and technology and marine economy in Guangdong maintains stable growth, but marine science and technology capabilities still need to be strengthened. On the one hand, the research reveals the development trend of Guangdong’s marine science and technology innovation and marine economy, and it provides a direction for the high-quality development of Guangdong’s marine economy. On the other hand, the research confirms the validity of the MGM(1,m) model and enriches the research field of grey forecasting models.
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- 2022
19. Chemical synthesis of glycans and applications in carbohydrate-based vaccines
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Yongshi Wang and Xin-Shan Ye
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chemistry.chemical_classification ,Glycan ,Glycosylation ,Glycobiology ,Glycoconjugate ,General Chemical Engineering ,Immunogenicity ,General Chemistry ,Biology ,Carbohydrate ,Polysaccharide ,Biochemistry ,Chemical synthesis ,chemistry.chemical_compound ,chemistry ,Materials Chemistry ,biology.protein - Abstract
Carbohydrates play important roles in many biological processes. However, the lack of resources of structurally-defined carbohydrates and their weak immunogenicity have always restricted the development of chemical glycobiology especially carbohydrate-based vaccines. The progress in chemical synthesis of carbohydrates and glycoconjugates has greatly promoted the development of carbohydrate-based vaccines including antibacterial vaccines, anti-tumor vaccines and anti-HIV vaccines. The use of one-pot glycosylation strategy and solid-phase glycosylation strategy is able to synthesize oligosaccharides and even polysaccharides more effectively than before. Glycoconjugates produced by combining the carbohydrate antigens and proper protein carriers improve the immunogenicity of carbohydrates. This review covers the general methods and strategies of carbohydrate chemical synthesis, and the recent development of carbohydrate-based vaccines, and also summarizes related work of our group, hoping to offer readers better understanding of chemical glycobiology especially carbohydrate-based vaccines.
- Published
- 2018
20. The Protective Effect of Cyanidin-3-Glucoside on Myocardial Ischemia-Reperfusion Injury through Ferroptosis
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Jing Chen, Zhiyang Lv, Xin Shan, Jie Wang, Meng-Jiao Yin, and Qinan Wu
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Male ,0301 basic medicine ,Autophagosome ,Aging ,Cardiotonic Agents ,Article Subject ,Cell Survival ,Iron ,Infarction ,Myocardial Reperfusion Injury ,Pharmacology ,medicine.disease_cause ,GPX4 ,Biochemistry ,Cell Line ,Anthocyanins ,Rats, Sprague-Dawley ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Endopeptidases ,Autophagy ,medicine ,Animals ,Ferroptosis ,QH573-671 ,Chemistry ,Myocardium ,Cell Biology ,General Medicine ,medicine.disease ,Oxygen ,Oxidative Stress ,Glucose ,030104 developmental biology ,030220 oncology & carcinogenesis ,Beclin-1 ,Ligation ,Cytology ,Perfusion ,Reperfusion injury ,Oxidative stress ,Research Article - Abstract
This study was conducted to estimate the protective effect of Cyanidin-3-glucoside (C3G) on myocardial ischemia-reperfusion (IR) injury and to explore its mechanism. The rats were subjected to left anterior descending ligation and perfusion surgery. In vitro experiments were performed on H9c2 cells using the oxygen-glucose deprivation/reoxygenation (OGD/R) model. The results showed the administration of C3G reduced the infarction area, mitigated pathological alterations, inhibited ST segment elevation, and attenuated oxidative stress and ferroptosis-related protein expression. C3G also suppressed the expressions of USP19, Beclin1, NCOA4, and LC3II/LC3I. In addition, treatment with C3G relieved oxidative stress, downregulated LC3II/LC3I, reduced autophagosome number, downregulated TfR1 expression, and upregulated the expressions of FTH1 and GPX4 in OGD/R-induced H9c2 cells. C3G could inhibit the protein levels of USP19 and LC3II. C3G promoted K11-linked ubiquitination of Beclin1. Further evidence that C3G reduced ferroptosis and ameliorated myocardial I/R injury was demonstrated with the ferroptosis promoter RSL3. Taken together, C3G could be a potential agent to protect myocardium from myocardial I/R injury.
- Published
- 2021
21. Proteomic analysis of healthy and atretic porcine follicular granulosa cells
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Ya Liu, Xiaoyu Guan, Fugui Fang, Yani Fan, Xin Shan, Yinghui Lin, Yunsheng Li, Yunhai Zhang, Xu Yan, Tong Yu, and Jianling Wu
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0301 basic medicine ,Proteomics ,endocrine system ,Swine ,Granulosa cell ,Follicular Atresia ,Biophysics ,Apoptosis ,Biology ,Biochemistry ,03 medical and health sciences ,Follicle ,Tandem Mass Spectrometry ,Follicular phase ,Animals ,Atretic Follicle ,Granulosa Cells ,030102 biochemistry & molecular biology ,Follicular atresia ,Antral follicle ,Cell biology ,030104 developmental biology ,Protein destabilization ,Female ,Signal transduction ,Chromatography, Liquid - Abstract
Follicular atresia is initiated with the apoptosis of granulosa cells (GCs) after birth in mammals. The molecular mechanisms underlying GC apoptosis during follicular selection are unclear at present. The objective of this study is to identify the proteins and pathways that may be involved in porcine follicular atresia. Proteins isolated from GCs collected from healthy and atretic follicles were detected by tandem mass tag (TMT) protein labeling and LC-MS/MS. A total of 4591 proteins in the healthy follicle granulosa cell (HFGC) and atretic follicle granulosa cell (AFGC) groups were identified, and 399 differentially abundant proteins were found between the HFGC and AFGC groups; of which 262 proteins were significantly up-regulated and 137 proteins were significantly down-regulated. Differential protein enrichment analysis showed that proteins involved in proteolysis, protein destabilization, phagocytosis, and engulfment were more abundant in the AFGC group. Also, these proteins were mainly involved in the lysosome, phagosome, autophagy, and apoptosis pathways. Specially, PTGFRN is potential important regulated protein in the development of the antral follicle, and down-regulation of PTGFRN in GCs may lead to follicular atresia. Our study shows that the identified proteins and their related signaling pathways may play crucial roles during health follicle develop to atretic follicle. SIGNIFICANCE: Follicular atresia during 'selection' reduces the reproductive potential of sows. In this study, we found 399 proteins differentially abundant. between the HFGC and AFGC groups. These results establish a foundation for elucidating the mechanism of follicular atresia in swine.
- Published
- 2020
22. Synthesis of N-Substituted Iminosugar Derivatives and Evaluation of Their Immunosuppressive Activities
- Author
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Xin-Shan Ye, Zhuo Lv, Youhong Niu, Qin Li, and Chengcheng Song
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Male ,Iminosugar ,Pharmacology ,Alkylation ,010402 general chemistry ,Inhibitory postsynaptic potential ,01 natural sciences ,Biochemistry ,Interferon-gamma ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Amide ,Drug Discovery ,Splenocyte ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,IC50 ,Cells, Cultured ,Cell Proliferation ,Mice, Inbred BALB C ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Imino Sugars ,0104 chemical sciences ,Molecular Medicine ,Interleukin-4 ,Immunosuppressive Agents ,Spleen - Abstract
It is important to find more effective and safer immunosuppressants, because clinically used immunosuppressive agents have significant side effects. A series of N-substituted iminosugar derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The results revealed that iminosugars 10 e and 10 i, that is, (3R,4S)-1-(4-heptyloxylphenylethyl)pyrrolidine-3,4-diol and (3R,4S)-1-[2-(2-chloro-4-(p-tolylthio)-phenyl-1-yl)ethyl]pyrrolidine-3,4-diol, respectively, exhibited the strongest inhibitory effects on mouse splenocyte proliferation (IC50 =2.16 and 2.48 μm, respectively), whereas the iminosugars containing an amide group near the hydrophilic head (compounds 10 j-n) exhibited no inhibitory effects. Further studies revealed that the inhibitory effects on splenocyte proliferation may have come from the suppression of both IFN-γ and IL-4 cytokines. Our results suggest that synthetic iminosugars, especially compounds 10 e and 10 i, hold potential as immunosuppressive agents.
- Published
- 2018
23. Chemical synthesis and biological evaluation of penta- to octa- saccharide fragments of Vi polysaccharide fromSalmonella typhi
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Meng-Man Wei, Xin-Shan Ye, Gao-Lan Zhang, De-Cai Xiong, Yu-Feng Ma, Chengcheng Song, and Xiu-Jing Zheng
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Pentamer ,Organic Chemistry ,Glycoside ,Oligosaccharide ,010402 general chemistry ,Salmonella typhi ,Polysaccharide ,01 natural sciences ,Chemical synthesis ,Epitope ,0104 chemical sciences ,Biochemistry ,Conjugate vaccine - Abstract
Vi antigen is the capsular polysaccharide of Salmonella typhi, which can cause typhoid fever. With the increasing threat of antiboitic resistance, vaccination against Salmonella typhi is a preferred way to prevent this disease. Chemical synthesis of fragments of Vi antigen is in urgent need for the development of structure-homogeneous and quality-controlled oligosaccharide vaccines. However, it is extremely challenging to synthesize large oligosaccharide fragments of Vi antigen owing to the exclusive α-1,4-linkage of polyaminogalacturonates. Herein, a series of Vi oligosaccharides ranging from pentamer to octamer were efficiently prepared using 2,3-N,O-oxazolidinone protected glycosides as building blocks based on the preactivation protocol. The heptasaccharide and octasaccharide fragments were synthesized for the first time. The competitive ELISA evaluation suggested that the hexasaccharide might be the minimum epitope of Vi antigen, which provides a significant guidance for the future development of Vi oligosaccharide vaccines.
- Published
- 2018
24. Validation, Identification, and Biological Consequences of the Site-specific O-GlcNAcylation Dynamics of Carbohydrate-responsive Element-binding Protein (ChREBP)
- Author
-
Xin-Shan Ye, An-Qi Yang, Daoyuan Li, and Lianli Chi
- Subjects
Threonine ,0301 basic medicine ,Acylation ,Active Transport, Cell Nucleus ,Receptors, Cytoplasmic and Nuclear ,Basic helix-loop-helix leucine zipper transcription factors ,Plasma protein binding ,Karyopherins ,N-Acetylglucosaminyltransferases ,Biochemistry ,Mass Spectrometry ,Cell Line ,Analytical Chemistry ,Cell-free system ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Transcription (biology) ,Serine ,Animals ,Phosphorylation ,Binding site ,Carbohydrate-responsive element-binding protein ,Nuclear export signal ,Molecular Biology ,Binding Sites ,Cell-Free System ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Chemistry ,Research ,Nuclear Proteins ,Cell biology ,Glucose ,030104 developmental biology ,14-3-3 Proteins ,Hepatocytes ,Protein Processing, Post-Translational ,030217 neurology & neurosurgery ,Protein Binding ,Transcription Factors - Abstract
O-GlcNAcylation of carbohydrate-responsive element-binding protein (ChREBP) is believed as an important modulator of ChREBP activities, however little direct evidence of O-GlcNAcylation on ChREBP and no exact O-GlcNAcylation sites have been reported so far. Here, we validate O-GlcNAcylation on ChREBP in cell-free coupled transcription/translation system and in cells by chemoenzymatic and metabolic labeling, respectively. Moreover, for the first time, we identify O-GlcNAcylation on Ser614 in the C-terminus of ChREBP by mass spectrometry and validate two important sites, Thr517 and Ser839 for O-GlcNAcylation and their function via molecular and chemical biological method. Under high glucose conditions, Ser514 phosphorylation enhances ChREBP O-GlcNAcylation, maintaining the transcriptional activity of ChREBP; Ser839 O-GlcNAcylation is essential for Mlx-heterodimerization and DNA-binding activity enhancement, consequently inducing transcriptional activity. Ser839 O-GlcNAcylation is also crucial for ChREBP nuclear export partially by strengthening interactions with CRM1 and 14-3-3. This work is a detailed study of ChREBP O-GlcNAcylation and highlights the biological consequences of the site-specific O-GlcNAcylation dynamics of ChREBP.
- Published
- 2017
25. General Approach to Five-Membered Nitrogen Heteroaryl C-Glycosides Using a Palladium/Copper Cocatalyzed C–H Functionalization Strategy
- Author
-
Shuo Zhang, Xin-Shan Ye, and Youhong Niu
- Subjects
C glycosides ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Copper ,Nitrogen ,0104 chemical sciences ,Yield (chemistry) ,Organic chemistry ,Surface modification ,Physical and Theoretical Chemistry ,Palladium - Abstract
A general approach to the synthesis of diverse heteroaryl-C-Δ1,2-glycosides has been developed by employing the Pd(OAc)2/CuI cocatalyzed direct cross-coupling of five-membered nitrogen heterocycles with 1-iodoglycals in a C–H activation manner. Using this method, 27 examples of heteroaryl-C-Δ1,2-glycosides, containing indoles, thiazoles, benzothiazoles, imidazoles, benzimidazoles, and benzoxazoles as aglycones were obtained in 43–99% yield.
- Published
- 2017
26. Synthesis and biological evaluation of N-arylated-lactam-type iminosugars as potential immunosuppressive agents
- Author
-
Youhong Niu, Qin Li, Chengcheng Song, Xin-Shan Ye, Hai-Qian Liu, and Tao Li
- Subjects
Drug ,Lactams ,media_common.quotation_subject ,Molecular Conformation ,Iminosugar ,Pharmacology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Jurkat Cells ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Splenocyte ,Animals ,Humans ,Structure–activity relationship ,MTT assay ,Physical and Theoretical Chemistry ,IC50 ,Cell Proliferation ,media_common ,Dose-Response Relationship, Drug ,010405 organic chemistry ,Chemistry ,Cell growth ,Organic Chemistry ,Combinatorial chemistry ,Imino Sugars ,0104 chemical sciences ,Lactam ,Immunosuppressive Agents ,Spleen - Abstract
Since the immunosuppressive agents currently used in clinics have significant side effects, it is very important to search for new effective and safe immunosuppressants. Iminosugars as a new class of immunosuppressants are less explored. In this report, 24 new N-arylated iminosugar derivatives, including d-talo and d-galacto epimers, were designed and synthesized, and their immunosuppressive effects were evaluated by MTT assay. The experimental data demonstrated that compound 20 showed the strongest inhibition effect (IC50 = 6.94 μM). Further studies revealed that the inhibitory effects on splenocyte proliferation may come from the suppression of both IFN-γ and IL-4 cytokines. The preliminary structure-activity relationship (SAR) analysis suggested that N-arylated d-galacto-type iminosugars showed better inhibitory activities than d-talo-type analogues. The SAR analysis also showed that the inhibition effect of iminosugars can be improved by decreasing the polarity or increasing the hydrophobicity. These results may be beneficial to the discovery of new iminosugar derivatives as immunosuppressive agents.
- Published
- 2017
27. Fluorine-modified sialyl-Tn-CRM197 vaccine elicits a robust immune response
- Author
-
Xin-Shan Ye, Yifa Zhou, Haili Guo, Fan Zhang, Qin Li, Chengcheng Song, Xiu-Jing Zheng, and Yafei Cao
- Subjects
Halogenation ,Antibodies, Neoplasm ,medicine.medical_treatment ,Gene Expression ,Lymphocyte proliferation ,Biochemistry ,Mice ,Immunogenicity, Vaccine ,Cancer immunotherapy ,Lymphocytes ,Th1-Th2 Balance ,Antibody-dependent cell-mediated cytotoxicity ,0303 health sciences ,Immunity, Cellular ,Mice, Inbred BALB C ,Chemistry ,Immunogenicity ,030302 biochemistry & molecular biology ,surgical procedures, operative ,Colonic Neoplasms ,Female ,therapeutics ,Adjuvant ,Cancer Vaccines ,03 medical and health sciences ,Interferon-gamma ,Immune system ,Antigen ,Adjuvants, Immunologic ,Bacterial Proteins ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Antigens, Tumor-Associated, Carbohydrate ,Molecular Biology ,030304 developmental biology ,Immune Sera ,Antibody-Dependent Cell Cytotoxicity ,Cell Biology ,nervous system diseases ,Immunity, Humoral ,nervous system ,Humoral immunity ,Cancer research ,Immunization ,sense organs ,Interleukin-4 ,Glycoconjugates ,Spleen - Abstract
Even though a vaccine that targets tumor-associated carbohydrate antigens on epithelial carcinoma cells presents an attractive therapeutic approach, relatively poor immunogenicity limits its development. In this study, we investigated the immunological activity of a fluoro-substituted Sialyl-Tn (F-STn) analogue coupled to the non-toxic cross-reactive material of diphtheria toxin197 (CRM197). Our results indicate that F-STn-CRM197 promotes a greater immunogenicity than non-fluorinated STn-CRM197. In the presence or absence of adjuvant, F-STn-CRM197 remarkably enhances both cellular and humoral immunity against STn by increasing antigen-specific lymphocyte proliferation and inducing a mixed Th1/Th2 response leading to production of IFN-γ and IL-4 cytokines, as well as STn-specific antibodies. Furthermore, antisera produced from F-STn-CRM197 immunization significantly recognizes STn-positive tumor cells and increases cancer cell lysis induced by antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) pathways. Our data suggest that this F-STn vaccine may be useful for cancer immunotherapy and possibly for prophylactic prevention of cancer.
- Published
- 2019
28. Anti-depressant effects of oil from fructus gardeniae via PKA-CREB-BDNF signaling
- Author
-
Qiang Fu, Jie Ruan, Xin Shan, Li Liu, and Baomei Xia
- Subjects
0301 basic medicine ,Biophysics ,Gardenia jasminoides ,Pharmacology ,CREB ,Biochemistry ,Hippocampus ,Pathogenesis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Western blot ,medicine ,Hippocampus (mythology) ,Animals ,Plant Oils ,Ketamine ,Medicine, Chinese Traditional ,Protein kinase A ,Cyclic AMP Response Element-Binding Protein ,Molecular Biology ,Research Articles ,Brain-derived neurotrophic factor ,Sulfonamides ,Plants, Medicinal ,biology ,medicine.diagnostic_test ,Behavior, Animal ,Chemistry ,Depression ,Brain-Derived Neurotrophic Factor ,Cell Biology ,Gardenia jasminoides oil extract ,biology.organism_classification ,Gardenia ,Isoquinolines ,Cyclic AMP-Dependent Protein Kinases ,Disease Models, Animal ,030104 developmental biology ,Gene Expression Regulation ,Fruit ,biology.protein ,030217 neurology & neurosurgery ,PKA/CREB/BDNF ,medicine.drug ,Research Article - Abstract
The dried ripe fruit of Gardenia jasminoides Ellis was usually applied as an herb medicine in Traditional Chinese Medicine. It was suggested that the Gardenia jasminoides oil extract (oil from Fructus Gardeniae [OFG]) might serve as a potential treatment for depression, whereas its pathogenesis still remained not fully understood. The present research was conducted to evaluate the anti-depressive effect of OFG in mice and explore its potential mechanism. The OFG and ketamine (KET) were intragastrically and intraperitoneally treated, respectively. Thereafter, the animals were subjected to the behavior tests. The expressions of protein kinase A (PKA), brain derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB) in hippocampus were detected by Western blot. The selective PKA inhibitor H-89 was also applied to confirm the mechanism. As a result, OFG and KET treatment improved the behavior performance. Furthermore, the administrations of OFG effectively enhanced the expressions of PKA, p-CREB, and BDNF. With the application of selective PKA inhibitor H-89, the ameliorated effects caused by OFG were blocked, but not by KET. In conclusion, the presented work indicated that OFG-exerted protective effect on depression through PKA-CREB-BDNF signaling.
- Published
- 2019
29. A general approach to C-Acyl glycosides via palladium/copper Co-catalyzed coupling reaction of glycosyl carbothioates and arylboronic acids
- Author
-
Li-Na Wang, Qing-Hui Cai, Youhong Niu, Xin-Shan Ye, and Qin Li
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Substrate (chemistry) ,chemistry.chemical_element ,Glycoside ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Copper ,Combinatorial chemistry ,Coupling reaction ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Glycosyl ,Palladium - Abstract
A general and efficient approach to the synthesis of various C-acyl glycosides has been developed via Pd2(dba)3/CuTC co-catalyzed cross-coupling reaction of glycosyl carbothioates with arylboronic acids. The reaction showed a broad substrate scope and 25 examples were exhibited in 61%–97% isolated yields. Furthermore, this reaction was applied to the gram-scale preparation of C-acyl glycosides. The coupled products can be further transformed into diverse biologically useful compounds, as exemplified by the synthesis of protected sergliflozin-A mimics.
- Published
- 2021
30. 3-Butenyloxycarbonyl as a new hydroxyl protecting group in carbohydrate synthesis
- Author
-
Xin-Shan Ye, Youhong Niu, and Nana Zeng
- Subjects
Glycosylation ,010405 organic chemistry ,Organic Chemistry ,Carbohydrate synthesis ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Organic chemistry ,Oxidative cleavage ,Protecting group - Abstract
3-Butenyloxycarbonyl (Bloc) has been identified as a new hydroxyl protecting group, which can be introduced under mild conditions in high yields and selectively removed by OsO4/NaIO4/2,6-lutidine in CH3CN–H2O without affecting most commonly-used protecting groups. Moreover, this new protecting group is inert under glycosylation conditions.
- Published
- 2016
31. Altering the Specificity of the Antibody Response to HIV gp120 with a Glycoconjugate Antigen
- Author
-
Canjia Zhai, Xin-Shan Ye, Chang-Cheng Liu, and Xiu-Jing Zheng
- Subjects
0301 basic medicine ,Glycan ,Glycoconjugate ,Oligosaccharides ,HIV Antibodies ,HIV Envelope Protein gp120 ,01 natural sciences ,Biochemistry ,Epitope ,Mannans ,Affinity maturation ,Epitopes ,03 medical and health sciences ,Antigen ,Animals ,Antigens ,AIDS Vaccines ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Vaccines, Synthetic ,biology ,010405 organic chemistry ,Antibodies, Monoclonal ,Serum Albumin, Bovine ,General Medicine ,HIV envelope protein ,Antibodies, Neutralizing ,Virology ,0104 chemical sciences ,030104 developmental biology ,Immunization ,chemistry ,Antibody Formation ,Immunology ,biology.protein ,Molecular Medicine ,Cattle ,Female ,Antibody ,Glycoconjugates ,Broadly Neutralizing Antibodies - Abstract
Some conserved glycans on the HIV envelope protein are targets of broadly neutralizing antibodies (bnAbs) of HIV. BnAbs provide a precise definition of broadly neutralizing epitopes on the envelope protein of HIV. These epitopes are promising for vaccine design. Many glycan-related antigens with high affinity to bnAbs have been tested as immunogens in vivo. However, it was found that no bnAb-like antibodies were induced. Vaccination with different immunogens containing the same neutralizing epitope may enhance the affinity maturation of antibodies which focus on the shared epitope. This combined immunization strategy showed great potential in peptide epitope-based vaccine design. However, it has not yet been explored on glycan-related epitopes to date. Herein, we take 2G12 as a model to validate this strategy on glycan-related epitopes. A high-affinity antigen of 2G12 was constructed by conjugating the D1 arm tetramannoside to bovine serum albumin. Then, the glycoconjugate was coimmunized with a recombinant gp120, which was expected to selectively benefit the induction of antibodies recognizing the neutralizing epitope of 2G12 on gp120. Mice were inoculated with the two antigens simultaneously or alternately to determine the suitable regimen for this strategy. The serological assays demonstrated that the antibody titers and subtypes responded to the whole gp120 were not improved, and the proportion of antibodies competitively bound to the 2G12 epitope was not enhanced significantly either. However, the coimmunized glycoconjugate selectively raised the proportion of antibodies recognizing D1 arm tetramannoside-related structures on gp120. These results provide important experience for the design of glycan-dependent bnAb-based vaccines.
- Published
- 2016
32. A new GLP-1 analogue with prolonged glucose-lowering activity in vivo via backbone-based modification at the N-terminus
- Author
-
Xin-Shan Ye, Youhong Niu, Yan-Fen Wu, Jingjing Zhu, An-Qi Yang, and Xiaohui Bai
- Subjects
Blood Glucose ,0301 basic medicine ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Endogeny ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Dipeptidyl peptidase ,03 medical and health sciences ,chemistry.chemical_compound ,Glucagon-Like Peptide 1 ,In vivo ,Amide ,Drug Discovery ,Humans ,Hypoglycemic Agents ,GLP-1 Analogue ,Receptor ,Molecular Biology ,Molecular Structure ,Chemistry ,Organic Chemistry ,In vitro ,0104 chemical sciences ,N-terminus ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Molecular Medicine - Abstract
Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogues 2–6 were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the β-peptide replacement strategy was used and analogues 7–13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.
- Published
- 2016
33. Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines
- Author
-
Chengcheng Song, Xiu-Jing Zheng, An Xiao, Xin-Shan Ye, Yue Gui, and Chang-Xin Huo
- Subjects
Synthetic vaccine ,010402 general chemistry ,Cancer Vaccines ,digestive system ,01 natural sciences ,Biochemistry ,Mice ,Antigen ,Cell Line, Tumor ,Neoplasms ,Animals ,Humans ,Antigens, Tumor-Associated, Carbohydrate ,Physical and Theoretical Chemistry ,skin and connective tissue diseases ,neoplasms ,MUC1 ,chemistry.chemical_classification ,Mice, Inbred BALB C ,biology ,010405 organic chemistry ,Chemistry ,Immune Sera ,Immunogenicity ,Mucin-1 ,Organic Chemistry ,Glycopeptides ,digestive system diseases ,biological factors ,Glycopeptide ,0104 chemical sciences ,Hemocyanins ,biology.protein ,Female ,Immunization ,Antibody ,Glycoprotein ,Keyhole limpet hemocyanin - Abstract
Glycoprotein MUC1 is an attractive target for anti-tumor vaccine development. However, the weak immunogenicity of MUC1 remains a significant problem. To solve this problem, several STn derivatives with N-acetyl modifications were synthesized and incorporated into a 20-amino acid MUC1 tandem repeat sequence. The modified STn-MUC1 glycopeptides were further connected to a carrier protein keyhole limpet hemocyanin (KLH). The immunological effects of these synthetic vaccine conjugates were evaluated using the BALB/c mouse model. The results showed that vaccine V2 elicited higher titers of antibodies which cross-reacted with the native STn-MUC1 antigen. Moreover, the elicited antisera reacted with the STn-MUC1 antigen-positive tumor cells, indicating that the carbohydrate antigen modification strategy may hold potential to overcome the weak immunogenicity of natural MUC1 glycopeptides.
- Published
- 2016
34. Indolo-quinoline boron difluoride dyes: synthesis and spectroscopic properties
- Author
-
Xiao-Ping Cao, Xin-Shan Ye, Xiaojun Yao, Hui-Xin Luo, Youhong Niu, and Xiaojie Jin
- Subjects
010405 organic chemistry ,Organic Chemistry ,Quinoline ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Biochemistry ,Fluorescence ,0104 chemical sciences ,chemistry.chemical_compound ,Suzuki reaction ,chemistry ,Boron difluoride ,Physical and Theoretical Chemistry - Abstract
Novel indolo-quinoline compounds were efficiently prepared via a Povarov-type reaction, and the structures were further modified by a Suzuki coupling reaction. The corresponding BF2-rigidified complexes were prepared and their spectroscopic properties were characterized with large Stokes shifts (up to 211 nm) and up to near-infrared (NIR) wavelength (667 nm). The synthetic complexes could be used as new fluorescent dyes.
- Published
- 2016
35. Direct C–H Trifluoromethylation of Glycals by Photoredox Catalysis
- Author
-
De-Cai Xiong, Xin-Shan Ye, and Bang Wang
- Subjects
Hydrocarbons, Fluorinated ,Light ,Molecular Structure ,Trifluoromethylation ,Chemistry ,Organic Chemistry ,Photoredox catalysis ,Alkenes ,Photochemistry ,Methylation ,Biochemistry ,Catalysis ,Reagent ,Photocatalysis ,Molecule ,Moiety ,Glycosides ,Physical and Theoretical Chemistry ,Visible spectrum - Abstract
A mild, efficient, and practical transformation for the direct C-H trifluoromethylation of glycals under visible light has been reported for the first time. This reaction employed fac-Ir(3+)(ppy)3 as the photocatalyst, Umemoto's reagent as the CF3 source, and a household blue LED or sunlight as the light source. Glycals bearing both electron-withdrawing and -donating protective groups performed this reaction smoothly. This visible light-mediated trifluoromethylation reaction was highlighted by the trifluoromethylation of the biologically important Neu2en moiety.
- Published
- 2015
36. Stereocontrolled Synthesis of 2-Deoxy- C-glycopyranosyl Arenes Using Glycals and Aromatic Amines
- Author
-
Shengbiao Tang, Qiannan Zheng, Xin-Shan Ye, Shende Jiang, De-Cai Xiong, and Qin Li
- Subjects
chemistry.chemical_compound ,010405 organic chemistry ,Chemistry ,Aryl ,Organic Chemistry ,Substrate (chemistry) ,Stereoselectivity ,Physical and Theoretical Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,0104 chemical sciences - Abstract
An efficient and stereoselective one-pot, two-step tandem α-arylation of glycals from readily available aryl amines via stable diazonium salts has been developed. Moreover, the stereoselective preparation of the challenging β- C-glycosyl arenes by the anomerization of α- C-glycosides using HBF4 is also described. This protocol has a broad substrate scope and a wide functional-group tolerance. It can be used for the gram-scale preparation of 3-oxo- C-glycosides, which are versatile substrates for the preparation of many biologically important C-glycosides.
- Published
- 2018
37. Frontispiece: Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides
- Author
-
Gao-Lan Zhang and Xin-Shan Ye
- Subjects
chemistry.chemical_classification ,Glycan ,chemistry ,biology ,Biochemistry ,Glycomimetic ,Organic Chemistry ,biology.protein ,General Chemistry ,Oligosaccharide ,Polysaccharide ,Catalysis - Published
- 2018
38. Rational Design of Dimeric Lysine N-Alkylamides as Potent and Broad-Spectrum Antibacterial Agents
- Author
-
Jianfeng Cai, Jianxing Hu, Yan-Fen Wu, Youhong Niu, Alekhya Nimmagadda, Cao Yafei, Xin-Shan Ye, and Minghui Wang
- Subjects
0301 basic medicine ,Staphylococcus aureus ,Gram-negative bacteria ,Cell Membrane Permeability ,Drug resistance ,Microbial Sensitivity Tests ,Gram-Positive Bacteria ,01 natural sciences ,Hemolysis ,Bacterial cell structure ,03 medical and health sciences ,chemistry.chemical_compound ,Antibiotic resistance ,Drug Resistance, Multiple, Bacterial ,Drug Discovery ,Gram-Negative Bacteria ,Escherichia coli ,Humans ,biology ,010405 organic chemistry ,Chemistry ,Lysine ,Rational design ,biology.organism_classification ,Small molecule ,Amides ,0104 chemical sciences ,Anti-Bacterial Agents ,030104 developmental biology ,Biochemistry ,Biofilms ,Drug Design ,Molecular Medicine ,Lead compound ,Bacteria - Abstract
Antibiotic resistance is one of the biggest threats to public health, and new antibacterial agents hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Utilizing dimerization strategy, we rationally designed and efficiently synthesized a new series of small molecule dimeric lysine alkylamides as mimics of AMPs. Evaluation of these mimics against a panel of Gram-positive and Gram-negative bacteria including MDR strains was performed, and a broad-spectrum and potent compound 3d was identified. This compound displayed high specificity toward bacteria over mammalian cell. Time-kill kinetics and mechanistic studies suggest that compound 3d quickly eliminated bacteria in a bactericidal mode by disrupting bacterial cell membrane. In addition, lead compound 3d could inhibit biofilm formation and did not develop drug resistance in S. aureus and E. coli over 14 passages. These results suggested that dimeric lysine nonylamide has immense potential as a new type of novel small molecular agent to combat antibiotic resistance.
- Published
- 2018
39. Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides
- Author
-
Xin-Shan Ye and Gao-Lan Zhang
- Subjects
Glycan ,Biocompatible Materials ,010402 general chemistry ,Polysaccharide ,01 natural sciences ,Catalysis ,Glycomimetic ,Polysaccharides ,medicine ,Carbohydrate Conformation ,Animals ,chemistry.chemical_classification ,Vaccines, Synthetic ,biology ,Bacteria ,010405 organic chemistry ,Heparin ,Organic Chemistry ,Polysaccharides, Bacterial ,Anticoagulants ,General Chemistry ,Oligosaccharide ,Carbohydrate ,0104 chemical sciences ,chemistry ,Biochemistry ,biology.protein ,Carbohydrate conformation ,Conjugate ,medicine.drug - Abstract
A large quantity of polysaccharide-derived conjugate vaccines have been developed to combat various pathogenic infections. Another prominent polysaccharide, heparin, is listed as an essential drug by the World Health Organization (WHO) to treat thrombus. One of their common problems is that they all derive from natural polysaccharides. Specifically, capsular polysaccharides are mainly obtained from bacterial fermentation and unfractionated heparin is extracted from animal tissues such as porcine mucosa. The quality of natural polysaccharides is inconsistent and traces of contamination would cause a disaster. By contrast, the use of chemical or chemoenzymatic methods could provide structurally homogeneous and quality-controlled glycans. To date, large numbers of polysaccharide fragments and their analogues have been synthesized and evaluated. Some of them even showed comparable activities to their corresponding natural polysaccharides. Here, the latest advances in these synthetic glycan analogues ranging from carbohydrate-based vaccines, heparin-related therapeutics and glycomimetics of polysaccharides are summarized.
- Published
- 2017
40. Synthesis of novel N-glycoside derivatives via CuSCN-catalyzed reactions and their SGLT2 inhibition activities
- Author
-
Xin-Shan Ye, Shao-Tao Bai, De-Cai Xiong, Youhong Niu, and Yan-Fen Wu
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,chemistry ,Stereochemistry ,Organic Chemistry ,Drug Discovery ,Triazole ,Click chemistry ,Glycoside ,Carbohydrate ,Biochemistry ,Coupling reaction ,Catalysis - Abstract
A convenient approach to the synthesis of novel triazole- N -glycoside derivatives was developed via CuSCN-catalyzed click reaction and Ullmann-type coupling reaction for the first time. The SGLT2 inhibitory activities of these synthetic N -glycosides were evaluated, and some compounds showed moderate SGLT2 inhibition activities at 100 nM. The results could benefit the discovery of new SGLT2 inhibitors for the treatment of diabetes.
- Published
- 2015
41. Synthetic phenylethanoid glycoside derivatives as potent neuroprotective agents
- Author
-
Yingguo Liu, Binhan Yu, Pu Xiaoping, Xin-Shan Ye, De-Cai Xiong, and Li Xiaxi
- Subjects
Drug ,Antioxidant ,Cell Survival ,media_common.quotation_subject ,medicine.medical_treatment ,Cell ,Chemistry Techniques, Synthetic ,PC12 Cells ,Neuroprotection ,Permeability ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Edaravone ,medicine ,Animals ,Glycosides ,media_common ,Pharmacology ,chemistry.chemical_classification ,Organic Chemistry ,Glycoside ,Free Radical Scavengers ,General Medicine ,Phenylethanoid ,Rats ,Neuroprotective Agents ,medicine.anatomical_structure ,nervous system ,chemistry ,Biochemistry ,Blood-Brain Barrier ,Drug Design ,Intracellular - Abstract
Several phenylethanoid glycoside derivatives were designed and synthesized. Most of the synthetic compounds showed significant neuroprotective effects, including antioxidative and anti-apoptotic properties. Specifically, target compounds displayed potent effects against various toxicities such as H2O2 and 6-hydroxydopamine (6-OHDA) in PC12 cells. Among the synthetic derivatives, three compounds (5, 6, 8) exhibited much superior activities to the marketed drug Edaravone. The compounds were able to prevent the 6-OHDA-induced damage in PC12 cells in a dose-dependent manner. The anti-apoptotic effects could be observed via cell morphological changes. Moreover, the compounds significantly reduced the intracellular ROS increase resulting from 6-OHDA treatment. The preliminary structure-activity relationships were also explored. Compounds 5, 6, 8 may hold the potential as promising neuroprotective agents and new lead compounds for the treatment of neurodegenerative diseases or cerebral ischemia.
- Published
- 2015
42. Additive-controlled stereoselective glycosylations of 2,3-oxazolidinone protected glucosamine or galactosamine thioglycoside donors with phenols based on preactivation protocol
- Author
-
Xin-Shan Ye, Qi Qin, and De-Cai Xiong
- Subjects
chemistry.chemical_classification ,Glucosamine ,Glycosylation ,Organic Chemistry ,Glycoside ,Galactosamine ,Stereoisomerism ,General Medicine ,Biochemistry ,Substrate Specificity ,Analytical Chemistry ,chemistry.chemical_compound ,Phenols ,chemistry ,Thioglycosides ,Phenol ,Organic chemistry ,Stereoselectivity ,Oxazolidinones - Abstract
Stereo-controllable glycosylation reactions of 2,3-oxazolidinone protected glucosamine thioglycoside donor with different phenol acceptors based on preactivation protocol, are described. It was found that BF3·Et2O worked as α-directing additive, while TTBP acted as β-directing additive. Simply by altering additives, either α-aryl glycosides or β-aryl glycosides were achieved in a stereoselective manner. The additives were also applied to the stereoselective glycosylation reactions of 2,3-oxazolidinone protected galactosamine donor with phenol substrates.
- Published
- 2015
43. Rapid determination of fenoldopam in human plasma by UPLC–MS/MS for pharmacokinetic analysis in patients
- Author
-
Guo-Dong He, Zhijie Zheng, Liping Mai, Chun-Yu Deng, Xipei Wang, Xi-Yong Yu, Zhi-Xin Shan, Qiu-Xiong Lin, Shi-Long Zhong, Min Yang, and Zhi-Ling Zhou
- Subjects
Fenoldopam ,Formic acid ,Liquid-Liquid Extraction ,Clinical Biochemistry ,Ethyl acetate ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Drug Stability ,Pharmacokinetics ,Limit of Detection ,Tandem Mass Spectrometry ,medicine ,Humans ,Chromatography, High Pressure Liquid ,Chromatography ,Elution ,Reproducibility of Results ,Cell Biology ,General Medicine ,chemistry ,Linear range ,Oxazepam ,Linear Models ,medicine.drug - Abstract
We developed and validated a rapid, selective, and sensitive ultra-performance liquid-chromatography mass-spectrometry (UPLC-MS/MS) method for quantifying fenoldopam in human plasma for pharmacokinetic studies. Fenoldopam and the internal-standard (IS), oxazepam, were isolated from human plasma by liquid-liquid extraction using ethyl acetate after alkalization, and were separated on a 2.1×100 mm Acquity UPLC HSS T3 C18 column (inside diameter, 1.8 μm) using a mobile phase of water (0.05% formic acid) and acetonitrile gradient elution. The fenoldopam and IS were eluted at 1.07 and 2.32 min, respectively. Quantification was performed using positive-ion electrospray-ionization (ESI), and the fenoldopam and IS responses were optimized at the m/z 306.16→107.10 and m/z 287.1→241.01 transitions, respectively. The assay was validated over the linear range of 0.1-40 ng/mL fenoldopam with intra- and interassay precision13.21%. The matrix effect of normal and hemolyzed plasma was 94.9-101.6%. Fenoldopam was stable for ≥34 days at -70 °C in normal and hemolyzed plasma containing ascorbic acid as a stabilizer. This method can be successfully applied in pharmacokinetic studies of fenoldopam in hypertensive patients.
- Published
- 2015
44. Synthetic and immunological studies of N-acyl modified S-linked STn derivatives as anticancer vaccine candidates
- Author
-
Chang-Cheng Liu, Xiu-Jing Zheng, Xin-Shan Ye, An Xiao, Chang-Xin Huo, Shuang Sun, and Zhuo Lv
- Subjects
Male ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Glycan ,biology ,Glycoconjugate ,Carbohydrate chemistry ,Immunogenicity ,Organic Chemistry ,Cancer Vaccines ,Biochemistry ,Antigen ,chemistry ,biology.protein ,Animals ,Antigens, Tumor-Associated, Carbohydrate ,Female ,Immunization ,Physical and Theoretical Chemistry ,Antibody ,Glycoconjugates ,Keyhole limpet hemocyanin ,Conjugate - Abstract
It is well known that tumor cells express some aberrant glycans, termed tumor-associated carbohydrate antigens (TACAs). TACAs are good targets for the development of carbohydrate-based anticancer vaccines. However, one of the major problems is that carbohydrate antigens possess a weak immunogenicity. To tackle this problem, a number of unnatural N-modified S-linked STn analogues were designed and prepared. Reaction of the modified STn disaccharides with bifunctional adipic acid p-nitrophenyl diester provided the corresponding activated esters, which was followed by the conjugation with keyhole limpet hemocyanin (KLH), affording the corresponding protein conjugates. The immunological properties of these glycoconjugates were evaluated in a mouse model. The results showed that the modified glycoconjugates stimulated the production of IgG antibodies that are capable of recognizing the naturally occurring STn antigen, helping the discovery of carbohydrate-based anticancer vaccine candidates.
- Published
- 2015
45. Rapid probing of sialylated glycoproteins in vitro and in vivo via metabolic oligosaccharide engineering of a minimal cyclopropene reporter
- Author
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Yang Yu, Hui-Xin Luo, Xin-Shan Ye, Cong Wang, Jingjing Zhu, De-Cai Xiong, Guihua Tai, Yuqian Ye, and Ming-Jie Han
- Subjects
Cyclopropanes ,Glycan ,Oligosaccharides ,Biochemistry ,Metabolic engineering ,Mice ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Labelling ,Animals ,Humans ,Physical and Theoretical Chemistry ,Glycoproteins ,chemistry.chemical_classification ,Staining and Labeling ,biology ,Organic Chemistry ,Oligosaccharide ,N-Acetylneuraminic Acid ,Sialic acid ,Metabolic Engineering ,chemistry ,Molecular Probes ,biology.protein ,Bioorthogonal chemistry ,Glycoprotein - Abstract
ManNAc analogues are important chemical tools for probing sialylation dynamically via metabolic oligosaccharide engineering (MOE). The size of N-acyl and the nature of the chemical handle are two determinants of metabolic incorporation efficiency. We demonstrated a minimal, stable, bioorthogonal, and reactive N-Cp (N-(cycloprop-2-ene-1-ylcarbonyl)) group and the imaging of sialylated glycans using Ac4ManNCp in vitro and in vivo. The results revealed that the Cp group can efficiently be incorporated into the cellular sialic acid and detected rapidly by the reaction with FITC-Tz in different cells. The metabolic incorporation efficiency of non-cytotoxic Ac4ManNCp is not only superior to Ac4ManNMCp, but also superior to the widely-used Ac4ManNAz in some cell lines. Moreover, when Ac4ManNCp was administered to mice, a rapid and intense labelling of splenocytes as well as glycoproteins of sera and organs was observed. This is the first reported metabolic labelling of cyclopropene-modified sugars in vivo. Therefore, Ac4ManNCp is a powerful probe for efficient and rapid MOE and it may find wide applications in the labelling of glycans.
- Published
- 2015
46. Synthesis of N-dialkylphosphoryl iminosugar derivatives and their immunosuppressive activities
- Author
-
Xin-Shan Ye, Guihua Tai, De-Cai Xiong, Xuemei Yang, and Chengcheng Song
- Subjects
Stereochemistry ,Iminosugar ,Biochemistry ,Interferon-gamma ,Mice ,Structure-Activity Relationship ,medicine ,Splenocyte ,Animals ,Structure–activity relationship ,Interferon gamma ,Secretion ,Physical and Theoretical Chemistry ,Alkyl ,Interleukin 4 ,Cell Proliferation ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,Imino Sugars ,chemistry ,Cytokine secretion ,Interleukin-4 ,Immunosuppressive Agents ,Spleen ,medicine.drug - Abstract
Twelve novel N-dialkylphosphoryliminosugar derivatives were synthesized and their immunosuppressive activities were evaluated on the proliferation of the mouse splenocytes and the secretion of IFN-γ and IL-4. The experimental data demonstrated that the iminosugars with the double long alkyl chains exhibited better inhibitory effects than those with the single long alkyl chain, and the iminosugars with the 10-carbon linear alkyl chain exhibited the strongest immunosuppressive activities. The assay of the cytokine secretion showed that the introduction of dialkyl chains on iminosugars could regulate the polarization of immune inhibition by varying the length of the alkyl chains. The disclosure of the structure-activity relationships may benefit the structural modifications of iminosugars to find new types of immunosuppressive agents.
- Published
- 2015
47. Discovery of Pentacyclic Triterpenoids as Potential Entry Inhibitors of Influenza Viruses
- Author
-
Yongying Shi, Yitao Wang, Han Wang, Maorong Yu, Yufei Wang, Zhihong Guo, Ge Fu, Longlong Si, Fei Yu, Pingxuan Jiao, Sulong Xiao, Yiming Wu, Demin Zhou, Lihe Zhang, Xin-Shan Ye, and Ke Tian
- Subjects
Models, Molecular ,Mice, Inbred BALB C ,Oseltamivir ,HEK 293 cells ,Hemagglutinin Glycoproteins, Influenza Virus ,Virology ,Triterpenes ,Virus ,In vitro ,Sialic acid ,Structure-Activity Relationship ,chemistry.chemical_compound ,HEK293 Cells ,Biochemistry ,Viral envelope ,chemistry ,Influenza A virus ,Docking (molecular) ,Drug Discovery ,Animals ,Humans ,Molecular Medicine ,Structure–activity relationship ,Administration, Intranasal - Abstract
Entry inhibitors are of particular importance in current efforts to develop a new generation of anti-influenza virus drugs. Here we report certain pentacyclic triterpenes exhibiting conserved structure features and with in vitro anti-influenza virus activity comparable to and even higher than that of oseltamivir. Mechanistic studies indicated that these lead triterpenoids bind tightly to the viral envelope hemagglutinin (HA), disrupting the interaction of HA with the sialic acid receptor and thus the attachment of viruses to host cells. Docking studies suggest that the binding pocket within HA for sialic acid receptor potentially acts as a targeting domain, and this is supported by structure-activity data, sialic acid competition studies, and broad anti-influenza spectrum as well as less induction of drug resistance. Our study might establish the importance of triterpenoids for development of entry inhibitors of influenza viruses.
- Published
- 2014
48. KOtBu-mediated aromatic O-glycosylation of 1,2-anhydrosugar and aryl boronic acid
- Author
-
Chen-Fu Liu, De-Cai Xiong, and Xin-Shan Ye
- Subjects
inorganic chemicals ,chemistry.chemical_classification ,Glycosylation ,010405 organic chemistry ,Aryl ,Organic Chemistry ,Glycoside ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Reagent ,Drug Discovery ,Organic chemistry ,Stereoselectivity ,Organic synthesis ,Boronic acid - Abstract
A new approach for the synthesis of phenolic glycosides via aromatic O-glycosylation of 1,2-anhydrosugar and aryl boronic acids was disclosed. This method is characterized by the use of aryl boronic acid as the aryl source and produces phenolic glycosides in a stereoselective manner. This reaction provides an alternative approach to the synthesis of phenolic glycosides. It also represents a new application of aryl boronic acids as versatile reagents in organic synthesis.
- Published
- 2016
49. Pilose antler peptide attenuates LPS-induced inflammatory reaction
- Author
-
Juanjuan Tang, Weiwei Tao, Li Liu, Yanyan Chen, Xin Shan, Baomei Xia, Yu Dong, and Xiaolan Cheng
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Lipopolysaccharides ,Cell Survival ,Inflammation ,Pharmacology ,Biochemistry ,Superoxide dismutase ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Structural Biology ,Malondialdehyde ,medicine ,Animals ,Protein kinase A ,Molecular Biology ,biology ,Superoxide Dismutase ,NF-kappa B ,NF-κB ,General Medicine ,Rats ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,biology.protein ,Cytokines ,Tumor necrosis factor alpha ,medicine.symptom ,Inflammation Mediators ,Mitogen-Activated Protein Kinases ,Peptides ,Nucleus ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
The present study was designed to study the effects of pilose antler peptide (PAP) on primary culture of nucleus pulposus cells in intervertebral disc. We demonstrated that PAP significantly inhibited lipopolysaccharides (LPS) induced over-production of inflammatory factors including interleukin-1β (IL-1β), tumor necrosis Factor-α (TNF-α) and interleukin-6 (IL-6) in nucleus pulposus cells. PAP also attenuated increase of malondialdehyde (MDA) and decrease of superoxide dismutase (SOD) induced by LPS challenge in a concentration-dependent manner. Moreover, the expression of the protein levels of mitogen-activated protein kinase (MAPK)/nuclear transcription factor-κB(NF-κB) were increased accompanying with the LPS challenge, which were significantly reversed after PAP treatment. Our results demonstrated the ability of PAP to antagonize LPS-mediated inflammation in primary culture of nucleus pulposus in intervertebral disc, suggesting a beneficial potential for its clinical application.
- Published
- 2017
50. Upscale production of a recombinant cyclodextrin glycosyltransferase from Paenibacillus macerans in Escherichia coli
- Author
-
Pi-Wu Wang, Wen-Xin Shan, and Yi-Nan Yang
- Subjects
Paenibacillus macerans ,chemistry.chemical_classification ,Cyclodextrin ,Cyclodextrin glycosyltransferase ,Environmental Science (miscellaneous) ,Biology ,medicine.disease_cause ,Agricultural and Biological Sciences (miscellaneous) ,carbohydrates (lipids) ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Tryptone ,medicine ,Glycerol ,Yeast extract ,Original Article ,Fermentation ,Escherichia coli ,Biotechnology - Abstract
Cyclodextrin glucanotransferase (CGTase) is an important enzyme with multiple functions in starch utilization. In the present study, a fermentation process for the production of CGTase from Escherichia coli harboring the recombinant plasmid pET28b(+)-CGTase was investigated and optimized. The optimal fermentation and expression conditions were 10.0 g/L glycerol, 20.0 g/L tryptone, and 10.0 g/L yeast extract with an initial pH of 7.0, an IPTG concentration of 0.1 mM and an induction temperature of 28 °C for 10 h. The resulting CGTase activity reached up to 36.4 U/L and was 2.1-fold higher than before optimization. Under these optimal fermentation conditions, the up-scaled fermentation was carried out in a 500-L fermentor, and a CGTase activity of 45.2 U/L was achieved. This study provides a foundation for the industrial production of CGTase.
- Published
- 2017
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