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On-line near-infrared spectroscopy optimizing and monitoring biotransformation process of γ-aminobutyric acid

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Journal of Pharmaceutical Analysis 2016年第3期6卷 171-178页

作者： Guoyu Ding Yuanyuan Hou Jiamin Peng Yunbing Shen Min Jiang Gang Bai State key laboratory of Medicinal Chemical Biology College of Pharmacy Nankai University Tianfin Key Laboratory of Molecular Drug Research Nankai University Tianjin 300071 China

Near-infrared spectroscopy （NIRS） with its fast and nondestructive advantages can be qualified for the real-time quantitative analysis. This paper demonstrates that NIRS combined with partial least squares （PLS） regression can be used as a rapid analytical method to simultaneously quantify L-glutamic acid （L- GIu） and γ-aminobutyric acid （GABA） in a biotransformation process and to guide the optimization of production conditions when the merits of NIRS are combined with response surface methodology. The high performance liquid chromatography （HPLC） reference analysis was performed by the o-phthaldialdehyde pre-column derivatization. NIRS measurements of two batches of 141 samples were firstly analyzed by PLS with several spectral pre-processing methods. Compared with those of the HPLC reference analysis, the resulting determination coefficients （R2）, root mean square error of prediction （RMSEP） and residual predictive deviation （RPD） of the external validation for the L-GIu concentration were 99.5%, 1.62 g/L, and 11.3, respectively. For the GABA concentration, R2, RMSEP, and RPD were 99.8%, 4.00 g/L, and 16.4, respectively. This NIRS model was then used to optimize the biotransformation process through a Box- Behnken experimental design. Under the optimal conditions without pH adjustment, 200 gjL L-GIu could be catalyzed by 7148 U/L glutamate decarboxylase （GAD） to GABA, reaching 99% conversion at the fifth hour. NIRS analysis provided timely information on the conversion from L-GIu to GABA. The results suggest that the NIRS model can not only be used for the routine profiling of enzymatic conversion, providing a simple and effective method of monitoring the biotransformation process of GABA, but also be considered to be an optimal tool to guide the optimization of production conditions.

关键词： Near-intrared spectroscopy L-glutamic acid γ-aminobutyric acid Box-Behnken design Glutamate decarboxylase

A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs

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Journal of Pharmaceutical Analysis 2021年第6期11卷 808-814页

作者： Ningning Tang Ling Li Fei Xie Ying Lu Zifan Zuo Hao Shan Quan Zhang Lianwen Zhang college of pharmacy and tianjin key laboratory of molecular drug research Nankai UniversityTianjin300350China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou510006China

Suppression of cellular O-linkedβ-N-acetylglucosaminylation(O-Glc NAcylation)can repress proliferation and migration of various cancer cells,which opens a new avenue for cancer *** on the regulation of insulin gene transcription,we designed a cell-based fluorescent reporter capable of sensing cellular O-Glc NAcylation in HEK293 T *** fluorescent reporter mainly consists of a reporter(green fluorescent protein(GFP)),an internal reference(red fluorescent protein),and an operator(neuronal differentiation 1),which serves as a"sweet switch"to control GFP expression in response to cellular OGlc NAcylation *** fluorescent reporter can efficiently sense reduced levels of cellular OGlc NAcylation in several cell *** the fluorescent reporter,we screened 120 natural products and obtained one compound,sesamin,which could markedly inhibit protein O-Glc NAcylation in He La and human colorectal carcinoma-116 cells and repress their migration in ***,the present study demonstrated the development of a novel strategy for anti-tumor drug screening,as well as for conducting gene transcription studies.

关键词： Fluorescent reporter High-throughput screening O-linkedβ-N-acetylglucosaminylation Anti-tumor drug Gene transcriptional regulation

Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

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Neural Regeneration research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang Feng Miao Peifeng Wei college of pharmacy and First Clinical Medical college Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National drug Clinical Trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

Design, synthesis and systematic evaluation of all possible cyclic dinucleotides (CDNs) that activate human stimulator of interferon genes (STING) variants

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Science China Chemistry 2020年第4期63卷 534-545页

作者： Zheng-Hua Wang Can-Can Zhao Qiang-Zhe Zhang Chuan-Lin Wang Hang Zhang De-Jun Ma Da-Wei Wang Xin Wen Lu-Yuan Li Zhen Xi State key laboratory of Elemento-organic Chemistry Department of Chemical BiologyCollege of ChemistryNankai UniversityTianjin 300071China State key laboratory of Medicinal Chemical Biology and college of pharmacy Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300071China Collaborative Innovation Center of Chemical Science and Engineering(tianjin) Tianjin 300071China National Pesticide Engineering research Center(tianjin) Tianjin 300071China

Cyclic dinucleotides(CDNs) are known to activate stimulator of interferon genes(STING) and induce type I interferon responses, therefor possess great potentials to be of immunotherapeutic value for cancers and infectious diseases. However, the existence of different single nucleotide polymorphism(SNP) of human STING(hSTING) gene poses an obstacle to achieve broad-spectrum activation by CDNs. We reported here the design and synthesis of a total of 36 CDNs, representing all structural variations, that contain four bases(A, G, C, U) and two linkage directions(2′-5′-linked and 3′-5′-linked phosphodiester).Through systematic evaluation of IFN-β induction with a dual-luciferase reporter assay, we discovered that wild type hSTING and two isoforms(HAQ and AQ) showed strong response while hSTING-R232 H and R293 Q exhibited the relatively weak response to CDNs stimulation. For the first time, we found that the c[G(2′,5′)U(2′,5′)] showed excellent activity against all five hSTING variants even equivalent to the endogenous ligand c[G(2′,5′)A(3′,5′)]. Furthermore, we have also demonstrated that 3′-3′CDNs with two 3′-5′ phosphodiesters showed higher serum and hydrolase stability than 2′-2′ CDNs with two 2′-5′ phosphodiesters and 2′-3′ CDNs with one 2′-5′ and one 3′-5′ phosphodiester. It is very interesting to note that 2′-2′ CDNs has been found for the first time to show strong activity. These findings will stimulate our exploration for the new functional role of CDNs, and provide guidelines to design CDNs based hSTING targeted drugs.

关键词： cyclic dinucleotides(CDNs) stimulator of interferon genes(STING) pyrimidine CDNs interferonβ ecto-nucleotide pyrophosphatase/phosphodiesterase 1(ENPP1)

Chemical proteomics reveals ligustilide targets SMAD3,inhibiting collagen synthesis in aortic endothelial cells

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Chinese Chemical Letters 2021年第1期32卷 190-193页

作者： Wei Lei Fukui Shen Nianwei Chang Lin Niu Yuanyuan Hou Boli Zhang Min Jiang Gang Bai State key laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300353China Institute of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

Atherosclerosis is a persistent inflammatory state,while vascular endothelial fibrosis is one of the primary causes of atherosclerosis *** ligustilide(Lig) was shown to exert obvious antiatherogenic effects in previous studies,its precise mechanism has not been deeply *** this paper,we designed a Lig-derived photoaffinity labelling(PAL) probe to identify potential therapeutic targets of Lig via chemical proteomics *** against decapentaplegic homologue 3(SMAD3),a signal transmitter of transforming growth factor-β(TGF-β) which promotes the development of vascular fibrosis,was identified as a potential target of *** suppressed the phosphorylation and nuclear translocation of SMAD3 by blocking the interaction between SMAD3 and TGF-β receptor 1,thereby inhibiting the collagen synthesis ***,developing a novel SMAD3 inhibitor may present a promising therapeutic option for preventing vascular fibrosis.

关键词： Ligustilide SMAD3 Collagen synthesis Chemical proteomics Photoaffinity labelling

Photochemical and Electrochemical Carbon Dioxide Utilization with Organic Compounds

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Chinese Journal of Chemistry 2018年第7期36卷 644-659页

作者： Yu Cao Xing He Ning Wang Hong-Ru Li Liang-Nian He State key laboratory and Institute of Elemento-Organic Chemistry College of Chemistry Collaborative Innovation Center of Chemical Science and Engineering Nankai University Tianjin 300071 China State key laboratory of Medicinal Chemical Biology and tianjin key laboratory of molecular drug research College of Pharmacy Nankai University Tianjin 300071 China

In the last few years, photochemical and electrochemical CO2 transformations have attracted increasing attention in response to topical interest in renewable energy and green chemistry. The present minireview offers an overview about the current approaches for the photochemical and electrochemical carbon dioxide fixation with organic compounds. Valuable products, including carboxylic acids and heterocyclic compounds, are accessible through carboxylation and carboxylative cyclization, respectively. In photochemical and electrochemical processes, photo- or electro-induced radical ions or other high-energy organic compounds are considered as key intermediates to react with CO2. Besides, activation of CO2 to produce radical anion has also been reported.

关键词： carbon dioxide carboxylative cyclization electrochemistry photocatalysis sustainable chemistry

Bioactivity-based UPLC/Q-TOF/MS strategy for screening of anti-inflammatory components from Cimicifugae Rhizoma

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Chinese Chemical Letters 2017年第2期28卷 476-481页

作者： Zeng-Yong Wang Qian Wang Yan-Qi Han Min Jiang Jie Gao Yan Miao Gang Bai State key laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University tianjin Engineering laboratory of Quality Control Technology of Traditional Chinese Medicine Tianjin Institute of Pharmaceutical Research The tianjin Engineering Center of Injection Package China Otsuka Pharmaceutical Company Limited

In this study,the protective effects of Cimicifugae Rhizoma（CR） was demonstrated in Pseudomonas aeruginosa-induced pneumonia mouse *** identify the anti-inflammatory ingredients,an ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）integrated nuclear factor κB（NF-κB） luciferase reporter assay screening system was carried *** a result,some caffeic acid derivatives,including caffeic acid,ferulic acid/isoferulic acid,fukinolic acid,and cimicifugic acid ingredients were identified as the potential effective compounds from *** testing the anti-inflammatory capacity,caffeic acid was demonstrated to inhibit NF-kB and reduce the levels of IL-6 and IL-8 in TNF-α-treated BEAS-2B cells in a dose-dependent ***,CR preparations and its cinnamic acid derivatives have the possibility to be developed as a complementary therapy in the treatment of respiratory system infection in clinics.

关键词： Cimicifugae Rhizoma Pseudomonas aeruginosa Pneumonia NF-κB Caffeic acid derivatives

gem-Dimethyl-bearing C-Glucosides as Sodium-glucose Co-transporter 2 （SGLT2） Inhibitors

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Chinese Journal of Chemistry 2011年第6期29卷 1192-1198页

作者： Shi, Yongheng Zhao, Guilong Lou, Yuanyuan Wang, Yuli Shao, Hua Liu, Wei Xu, Weiren Tang, Lida School of pharmacy Tianjin Medical University Tianjin 300070 China tianjin key laboratory of molecular Design and drug Discovery Tianjin Institute of Pharmaceutical Research Tianjin 300193 China college of Chemistry and molecular Engineering Qingdao University of Science and Technology Qingdao Shandong 266042 China

Three novel gem-dimethyl C-glucosides were designed as sodium-glucose co-transporter 2 （SGLT2） inhibitors, and their syntheses started from D-glucose and three 2-substituted-5-bromobenzoic acids were achieved via a facile 8-step protocol, with the key step being anhydrous aluminum chloride-catalyzed Friedel-Crafts alkylation of tertiary alcohols and phenetol. These three SGLT2 inhibitors were evaluated in vivo with a mice oral glucose tolerance test （OGTT）, and the anti-hyperglycemic activities of all these three compounds were comparable with that of the positive control Dapagliflozin.

关键词： sodium-glucose co-transporter 2 (SGLT2) gem-dimethyl synthesis Friedel-Crafts alkylation oral glucose tolerance test (OGTT)

Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang Department of Clinical pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina college of pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes