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Evolution of Monkeypox C9L RNA G-Quadruplex Elevates the Translation of Its Only Kelch-like Protein by Accelerating G-Quadruplex Unfolding Kinetics

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CCS Chemistry 2024年第4期6卷 953-963页

作者： Yicong Dai Xucong Teng Difei Hu Qiushuang Zhang Jinghong Li department of Chemistry Center for Bioanalytical ChemistryKey Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologyTsinghua UniversityBeijing 100084 New Cornerstone Science Laboratory Shenzhen 518054 Beijing Life Science Academy Beijing 102209 Center for bioanalytical Chemistry Hefei National Laboratory of Physical Sciences at the MicroscaleUniversity of Science and Technology of ChinaHefei 230026

Genomic surveillance of monkeypox virus(MPXV)is essential to explore the reason of its unusual *** phylogenomic analysis of the MPXV genome mainly focuses on the effect of amino acid ***,we explore the evolutionary variation of RNA G-quadruplex(RG4)of MPXV and find that the genome evolution of MPXV can also produce new effects through changes in the RG4 *** RG4 is located in MPXV’s only Kelch-like C9L gene,which encodes for an antagonist of the innate immune *** evolution of this virus increases the unfolding kinetic constant of C9L RG4 and promotes the C9 protein level in living ***,all reported MPXV genomes in 2022 carry the C9L-RG4-5 pattern with the highest unfolding kinetic ***,the RG4 ligand,RGB-1,can impede the unfolding of C9L-RG4-5 and thereby reduce the C9 protein *** findings carve out a new path to comprehensively understanding MPXV virology.

关键词： G-quadruplex RNA secondary structure unfolding kinetics monkeypox virus genomic evolution immune evasion

Real-time identification of multiple nanoclusters with a protein nanopore in single-cluster level

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Nano Research 2024年第1期17卷 262-269页

作者： Ling Zhang Peilei He Huang Chen Qingda Liu Libo Li Xun Wang Jinghong Li department of Chemistry Center for BioAnalytical ChemistryKey Laboratory of Bioorganic Phosphorus Chemistry&Chemical BiologyTsinghua UniversityBeijing 100084China School of Chemistry and Chemical Engineering Guangdong Prov Key Lab Green Chem Prod TechnolSouth China University of TechnologyGuangzhou 510640China New Cornerstone Science Laboratory Shenzhen 518054China Beijing Institute of Life Science and Technology Beijing 102206China Center for bioanalytical Chemistry Hefei National Laboratory of Physical Science at MicroscaleUniversity of Science and Technology of ChinaHefei 230026China

It is important and challenging to analyze nanocluster structure with atomic ***,α-hemolysin nanopore was used to identify nanoclusters at the single molecule level by providing two-dimensional(2D)dwell time–current blockage spectra and translocation event frequency which sensitively depended on their *** such as Anderson,Keggin,Dawson,and a few lacunary Dawson polyoxometalates with very similar structures,even with only a two-atom difference,could be *** nanopore device could simultaneously measure multiple nanoclusters in a mixture qualitatively and ***,molecular dynamics(MD)simulations provided microscopic understandings of the nanocluster translocation dynamics and yielded 2D dwell time–current blockage spectra in close agreement with *** nanopore platform provides a novel powerful tool for nanocluster characterization.

关键词： nanopore single-molecule nanocluster polyoxometalates real-time detection

Development of an active-site titrant for SARS-CoV-2 main protease as an indispensable tool for evaluating enzyme kinetics

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2349-2357页

作者： Rabea Voget Julian Breidenbach Tobias Claff Alexandra Hingst Katharina Sylvester Christian Steinebach Lan Phuong Vu Renato H.Weiße Ulrike Bartz Norbert Sträter Christa E.Müller Michael Gütschow Pharmaceutical Institute Pharmaceutical&Medicinal ChemistryUniversity of BonnBonn 53121Germany Institute of bioanalytical Chemistry Center for Biotechnology and BiomedicineLeipzig UniversityLeipzig 04103Germany department of Natural Sciences University of Applied Sciences Bonn-Rhein-SiegRheinbach 53359Germany

A titrant for the SARS-CoV-2 main protease(M^(pro))was developed that enables,for the first time,the exact determination of the concentration of the enzymatically active M^(pro) by active-site *** covalent binding mode of the tetrapeptidic titrant was elucidated by the determination of the crystal structure of the enzyme–titrant *** fluorogenic substrates of M^(pro),including a prototypical,internally quenched Dabcyl-EDANS peptide,were compared in terms of solubility under typical assay *** exploiting the new titrant,key kinetic parameters for the M^(pro)-catalyzed cleavage of these substrates were determined.

关键词： COVID-19 SARS-CoV-2 Main protease Peptide nitriles Fluorogenic substrates Active-site titration X-ray crystallography Inner filter effect

吲哚-3-乙酸,阿尔茨海默病的潜在治疗靶点（英文）

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Science Bulletin 2024年第2期 146-147页

作者：李景虹 department of Chemistry Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education) Center for bioanalytical Chemistry Tsinghua University

Alzheimer’s disease(AD) is a chronic and progressive neurodegenerative disease that is characterized by the presence of amyloid-β(Aβ) plaques, hyperphosphorylated microtubule-associated tau protein(p-tau) neurofibrillary tangles and neuronal degeneration. According to recent data, AD is the most common global cause of dementia in the elderly.

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Quantitation of tadalafil in human plasma using a sensitive and rapid LC-MS/MS method for a bioequivalence study

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Journal of Pharmaceutical Analysis 2018年第4期8卷 271-276页

作者： Abhaysingh Bhadoriya Bhavesh Dasandi Dharmesh Parmar Priyanka A. Shah Pranav S. Shrivastav bioanalytical department Synchron Research Services Pvt. Ltd. department of Chemistry School of Sciences Gujarat University

A highly sensitive liquid chromatography-tandem mass spectrometry（LC-MS/MS） method was developed for the determination of tadalafil（TAD） in human plasma. TAD and its deuterated internal standard（IS）, tadalafil-d3, were extracted from 200 mL plasma using Phenomenex Strata-X-C 33 m extraction cartridges. Chromatographic analysis was carried out on Synergi Hydro-RP C18（100 mm × 4.6 mm, 4 mm）column with a mobile phase consisting of methanol and 10 m M ammonium formate, p H 4.0（90：10, v/v）,delivered at a flow rate of 0.9 m L/min. Quantitation of the protonated analyte was done on a triple quadrupole mass spectrometer using multiple reaction monitoring via electrospray ionization. The precursor to product ions transitions monitored for TAD and TAD-d3 were m/z 390.3-268.2 and m/z393.1-271.2, respectively. The calibration curve was linear over the concentration range of 0.50–500 ng/m L with correlation coefficient, r2 Z 0.9994. Acceptable intra-batch and inter-batch precision（r3.7%） and accuracy（97.8% to 104.1%） were obtained at five concentration levels. The recovery of TAD from spiked plasma was highly precise and quantitative（98.95% to 100.61%）. Further, the effect of endogenous matrix components was minimal. TAD was found to be stable under different storage conditions in human plasma and also in whole blood samples. The validated method was successfully used to determine TAD plasma concentration in a bioequivalence study with 20 mg TAD tablets in 24 healthy volunteers. Method performance was evaluated by reanalyzing 115 study samples.

关键词： Tadalafil Tadalafil-d3 LC-MS/MS Sensitive Bioequivalence study Human plasma

Dynamics of dark-bright vector solitons in a birefringent fiber

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Chinese Optics Letters 2007年第9期5卷 504-506页

作者：李宏王东宁 Hubei Key Laboratory of bioanalytical Technique Hubei Normal University department of Electrical Engineering The Hong Kong Polytechnic University

Coupled dark-bright vector solitons are considered in a birefringent fiber, and their dynamics are studied by the variational approach. The stationary states are analyzed, and it is found that their intensity distribution depends strictly on the ratio of the group-velocity delay strength to the effective total energy. Finally, the propagation of the coupled dark-bright vector solitons is investigated by the numerical method.

关键词： Birefringence Dynamics Light propagation Numerical methods Optical fibers

Thermal Behavior and Non-isothermal Kinetics of the Polyoxometalate of Ciprofloxacin with Tungstophosphoric Acid

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Journal of Wuhan University of Technology(Materials Science) 2007年第2期22卷 240-244页

作者：汪敦佳 Hubei Key Laboratory of bioanalytical Technique Department of Chemistry and Environmental EngineeringHubei Normal University

The polyoxometalate （CPFX-HCl）3H3PW12O40·.8H2O was prepared and characterized by elemental analysis, IR spectra and TG-DTA-DTG. The thermal decomposition mechanism and non-isothermal kinetic parameters of the polyoxometalate were obtained from the analysis of TG-DTG data using the Achar equation, Coats-Redfern equation （CR）, Madhusudanan-Krishnan-Ninan equation （MKN） and Horowitz-Metzger equation （HM）. And their mathematical expressions of the kinetic compensation effect were also calculated.

关键词： non-isothermal kinetics thermal behavior polyoxometalate ciprofloxacin TG-DTA-DTG

Preparation and Properties of the Heteropolyoxometalates of Large Organic Cation with Molybdotungstosilicic Acids

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Journal of Wuhan University of Technology(Materials Science) 2008年第2期23卷 198-203页

作者： WANG Dunjia FANG Zhengdong WEI Xianhong Hubei Key Laboratory of bioanalytical Technique Department of Chemistry and Environmental Engineering Hubei Normal University Huangshi 435002 China

Some new heteropolyoxometalates of large organic cations with molybdotungstosilicic acids （general formula：（CTMA）4SiMoxW12-xO40·mH2O·nDMF, x=0,2,4,6,8,10,12） were prepared by the reaction of cetyltrimethylammonium bromide （CTMAB,C16H33N（CH3）3Br） with H4SiMoxW12-xO40（x=0,2,4,6,8,10,12） in aqueous solution and recrystallization in DMF, and characterized by elemental analysis, IR spectra,TG- DTA and XRD techniques. The IR spectrum confirms the presence of Keggin structure and organic cations in these compounds, and it is indicated that the stretching vibration of the M-Od, M-Ob-M and Si-Oa becomes more red-shifted when molybdenum is gradually substituted for the tungsten atom. In particular, the thermal decomposition of the heteropolyoxometalates was studied in nitrogen atmosphere. The TG-DTA curves show that their thermal behaviors not only contain the release of water molecule, DMF molecule, CTMA and its fragments but also contains simultaneous collapse of Keggin anion. Their end products of the thermal decomposition are the mixture of WO3, MoO3 and SiO2. And from the final decomposition temperature of view, it is found that the thermal stability of these compounds gradually is decreased when the number of molybdenum atoms is increased.

关键词： heteropolyoxometalates molybdotungstosilicic acid cetyltrimethylammonium bromide IR spectral and thermal study

Sensitive and rapid determination of amantadine without derivatization in human plasma by LC–MS/MS for a bioequivalence study

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Journal of Pharmaceutical Analysis 2018年第3期8卷 202-207页

作者： Abhaysingh Bhadoriya Shivprakash Rathnam Bhavesh DasANDi Dharmesh Parmar Mallika Sanyal Pranav S.Shrivastav bioanalytical department Synchron Research Services Pvt.Ltd department of Chemistry St.Xavier's College department of Chemistry School of Sciences Gujarat University

A highly sensitive, rapid and rugged liquid chromatography-tandem mass spectrometw （LC-ESI-MS/MS） method was developed for reliable estimation of amantadine （AMD）, an antiviral drug in human plasma. The analyte and internal standard （IS）, amantadine-d6 （AMD-d6）, were extracted from 200μL plasma by solid phase extraction on Phenomenex Strata-X-C 33 ~t cartridges. Chromatography was performed on Synergi^TM Hydro-RP C18 （150 mm×4.6 mm, 4 μm） analytical column using a mixture of acetonitrile and 10 mM ammonium formate, pH 3.0 （80：20, v/v） as the mobile phase. Detection and quantitation was done by multiple reaction monitoring in the positive ionization mode for AMD （m/z 152.1→ 135.1 ） and IS （m/z 158.0 → 141.1） on a triple quadrupole mass spectrometer. The assay was linear in the concentration range of 0.50-500 ng/mL with correlation coefficient （r^2）〉 0.9969. The limit of detection of the method was 0.18 ng/mL The intra-batch and inter-batch precisions were 〈 5.42% and the accuracy varied from 98.47% to 105.72%. The extraction recovery of amantadine was precise and quantitative in the range of 97.89%-100.28%. IS-normalized matrix factors for amantadine varied from 0.981 to 1.012. The stability of AMD in whole blood and plasma was evaluated under different conditions. The developed method was successfully applied for a bioequivalence study with 100 mg of AMD in 32 healthy volunteers. The reproducibility of the assay was determined by reanalysis of 134 subject samples.

关键词： Amantadine Amantadine-d6 LC-ESI-MS/MS Sensitive Bioequivalence study Human plasma