Simultaneous determination of ten nucleosides and bases in Ganoderma by micellar electrokinetic chromatography

Ganoderma(lingzhi)is a famous herbal medicine and edible supplement in oriental countries for a long history.In this study,a simple micellar electrokinetic chromatography(MEKC)method was established for the analysis of nucleosides and bases,the major bioactive components in Ganoderma for the first time.By optimizing the borate concentration,the sodium dodecyl sulfate(SDS)concentration and the pH value of running buffer,10 nucleosides and bases achieved an ideal separation.In real sample analysis,the developed method was successfully used to determine the 10 target analytes in 23 batches of Ganoderma samples from different regions.Results indicated that contents of 10 investigated analytes in each sample showed obvious variation.The principal components analysis(PCA)and hierarchical cluster analysis(HCA)analysis classified the samples into three groups,and the HCA tree visualized the relationships which was mainly contributed by geographical partition.The results indicated geographical origin to be an important factor that affect the accumulation of nucleosides and bases in Ganoderma.In summary,this study provides a simple and practical strategy for quality assessment and cultivation reference of Ganoderma.

STEREOCHEMISTRY IN CYCLOPHOSPHORYLATION OF NUCLEOSIDES

In the presence of tetrazole,2'-substituted nucleosidesreacted ster■os■ifi■ally with n-BuOPIN■_2H_5■_2I_2 to nucleoside 3',5'-■lopnosphites with avial n-Buo group.The stereochemistry of oxidation of■y■lophosphite was investigated.

A new method for inversion of hydroxyl group of carbocyclic nucleosides

The hydroxyl group of carbocyclic nucleosides was inversed when the compounds were treated with Me3SiCl, KCN and a catalytic mount of NaI in DMF/CH3CN.

Interaction between N-phosphoryl-α-,β-and γ-amino acids and nucleosides

The reactions of four different N-（O,O＇-diisopropyl） phosphoamino acids （DIPP-aa）, such as N-phosphoryl-L-α-alanine （DIPP- L-α-Ala）, N-phosphoryl-D-α-alanine （DIPP-D-α-A1a）, N-phosphoryl-β-alanine （DIPP-β-A1a） and N-phosphoryl-γ-amino butyric acid （DIPP-γ-Aba）, and four nucleosides, adenosine （A）, guanosine （G）, cytidine （C） and uridine （U）, were studied by electrospray ionization tandem mass spectrometry （ESI-MS/MS） and HPLC/ESI-MS. DIPP-L-α-A1a and DIPP-D-α-A1a produced the same phosphorylated nucleosides, dinucleotides and phosphoroligopeptide. However, DIPP-β-A1a and DIPP-γ-Aba gave no relevant products.

Nucleosides 10: Synthesis of New Derivatives of Pyrimidine and Fused Pyrimidine Nucleosides of Expected Biological Activity

Pyrimidines, such as 6-amino-2-thio and 2-methylthiouracils and fused pyrimidines, such as thienopyrimidines reacted with 1-O-acetyl-2,3,5-tri-O- benzoyl-β-D-ribofuranose to get new derivatives of the corresponding nucleosides. The obtained protected nucleosides were deprotected by methanolic sodium methoxide to get the corresponding free uracil and thienopyrimidine nucleosides. The new nucleosides formed were tested for biological activity against some of microorganism (some fungi and bacteria species). Some of the tested products showed moderate activity and the results were reported.

STEREOSELCETIVE SYNTHESIS OF SOME NUCLEOSIDES

A new method for the synthesis of perbenzylated, peracetylated and perbenzoylated sugar nucleosides has been carefully studied. In this method trichloroacetoxy and trifluoroacetoxy groups were displaced efficiently in the reaction of nucleoside formation as leaving group. And this method was found to be widely applicable in the study of carbohydrate chemistry.

Synthesis and X-Ray Structure of New Anticancer Nucleosides Based on 1-((2-Hydroxyethoxy)methyl)-5-(phenylthio)-1H-1,2,4-triazole-3-carboxamide

A pair of new anticancer nucleosides based on 1,2,4-triazole nucleosides and 1-((2-hydroxyethoxy) methyl)-5-(phenylthio)-1H-1,2,4-triazole-3-carboxamide have been synthesized, and have given the corresponding products in excellent yields. Its structures and conformations were confirmed by single crystal X-ray diffraction.

Design and Synthesis of Lipids Bearing Nucleosides as Gene Vectors

Some novel lipids bearing nucleosides were designed and synthesized as gene vectors, and the structures of these compounds were characterized by UV, IR, 1HNMR, 13CNMR and elemental analysis.

Graphene as adsorbent for highly efficient extraction of modified nucleosides in urine prior to liquid chromatography-tandem mass spectrometry analysis

RNA modifications have been involved in numerous biological processes, and aberrations of these modifications are tightly associated with various diseases including cancer. Herein, we developed graphenebased solid-phase extraction and robust ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) combined with stable isotope-dilution for simultaneous enrichment and accurate determination of 17 modified nucleosides in human urine. We found graphene could effectively adsorb various modified nucleosides in human urine samples. With this method, we identified and quantified these modified nucleosides in urine samples collected from lung cancer patients and healthy controls.We revealed that the levels of 12 modified nucleosides were all diminished in urine from lung cancer patients, compared with healthy controls. It is worth noting that we demonstrated, for the first time, the presence of 5,2-O-dimethyluridine(m~5U_m) in human urine. Together, we established a robust analytical method for simultaneous determinations of 17 modified nucleosides in human urine, and our results revealed a close correlation between the concentrations of urinary modified nucleosides and the occurrence of lung cancer, implying the potential applications of these modified nucleosides as noninvasive biomarkers for the early detection of lung cancer. Moreover, this study will stimulate future investigations on the regulatory roles of RNA modifications in the initiation and progression of lung cancer.

Catalyst-Free Regio-and Diastereoselective Synthesis of Heterocyclic Nucleosides in the Eco-friendly Solvent 2-Methyltetrahydrofurant

An efficient and practical synthesis of heterocyclic nucleosides is developed by a catalyst-free highly regioselective and diastereose-lective[3+2]annulation of a-purine-substituted acrylates with nitrones.The reaction operates with excellent functional group toler-ance,very mild reaction conditions,and with the green,sustainable,and eco-friendly 2-methyltetrahydrofuran(2-MeTHF)as sol-vent.Compared with other reactions of electron-deficient olefin dipolarophiles with nitrones,different regioselective cycloaddition products were observed in this work.This 1,3-dipolar cycloaddition reaction gives a series of isoxazolidinyl nucleosides in good to excellent yields with promising applications in biochemistry and medicinal chemistry.

Molecular Recognition of Bases and Nucleosides by Mono-substituted Mononuclear Complexes of 1,4,7,10-Tetraaza-cyclododecane

The mononuclear macrocyclic polyamine metal complexes 5a-5e have been shown to form stable 1:1 complexes with bases and nucleosides. Their binding constants (K) were determined by UV-visible spectrometric titration. The results show that recognition ability of the complexes 5a-5e for uracil, U (Uri-dine), dT (Thymidine) is higher than that for the other bases or nucleosides (such as Cytidine, Guanosine, Adenosine). The metal ion also plays an important role for the recognition ability of complexes.

Interaction of bis-aryl functionalized molecules with nucleosides and nucleic acids

A series of novel molecules with a cyclen(1,4,7,10-tetraazacyclododecane) moiety appended on and bearing different aromatic fragments in the structures were synthesized and characterized.The binding activities of these compounds towards DNA were systematically studied by spectroscopic,viscometric and gel electrophoresis methods.The results suggest that the stacking interaction plays an important role in improving the DNA binding ability of the compounds.The binding modes of the compounds towards DNA are also affected by the sizes of the aromatic rings.The binding interaction between binaphthyl compound 1b and several nucleosides was studied by fluorescence titration.Stacking interaction and hydrophobic interaction play the key role in such non-selective binding process.

Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors:A case report and literature analysis

Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.

A novel strain of Levilactobacillus brevis PDD-5 isolated from salty vegetables has beneficial effects on hyperuricemia through anti-inflammation and improvement of kidney damage

Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified with the function of alleviating hyperuricemia.The relevant effects of L.brevis PDD-5 in lowering uric acid were analyzed by in vitro and in vivo experiments.The results showed that the L.brevis PDD-5 has(68.86±15.46)%of inosine uptake capacity and(95.75±3.30)%of guanosine uptake capacity in vitro.Oral administration of L.brevis PDD-5 to hyperuricemia rats reduced uric acid,creatinine,and urea nitrogen in serum,as well as decreased inosine and guanosine levels in the intestinal contents of rats.Analysis of relevant markers in the kidney by ELISA kits revealed that L.brevis PDD-5 alleviated oxidative stress and inflammation.Moreover,the gene expression of uric acid transporter 1(URAT1)and glucose transporter 9(GLUT9)was down-regulated,and the gene expression of organic anion transporter 1(OAT1)was up-regulated after treatment with L.brevis PDD-5.Western blot analysis showed that L.brevis PDD-5 alleviated hyperuricemia-induced kidney injury through the NLRP3 pathway.The se findings suggest that L.brevis PDD-5 can lower uric acid,repair kidney damage,and also has the potential to prevent uric acid nephropathy.

Ortho-(1-phenylvinyl)benzyl glycosides: Ether-type glycosyl donors for the efficient synthesis of both O-glycosides and nucleosides

Both O-glycosides and nucleosides are essential biomolecules with important roles in a variety of biological processes.Chemical synthesis of both O-glycosides and nucleosides is a scalable and reliable method to develop new therapeutic agents and decipher their functions.However,the efficient synthesis of both O-glycosides and nucleosides remains one of long-standing challenges in chemical synthesis.In particular,ether-type glycosyl donors are rarely developed to achieve the efficient synthesis of both O-glycosides and nucleosides due to the stronger conditions required for breaking of the glycosidic C–O bond.Here we report that ortho-(1-phenylvinyl)benzyl glycosides are new ether-type donors for efficient synthesis of both O-glycosides and nucleosides under mild reaction conditions.This glycosylation method enables glycosylation with both alcoholic acceptors and nucleobases with a variety of reactive functionalities.Furthermore,the latent-active synthesis of glycans and the efficient synthesis of nucleosides antibiotics have also been successfully demonstrated in the current glycosylation protocol,thereby representing an important step toward streamlining the chemical synthesis of both O-glycosides and nucleosides.

Benign perfluoroalkylation of uracils and uracil nucleosides via visible light-induced photoredox catalysis

In this work, an efficient and facile method for the preparation of 5-perfluoroalkylation uracils and uracil nucleosides through visible-light-mediated reaction has been developed. The reaction processes in high efficiency under mild reaction conditions and show broad substrate scope by employing commercial available perfluoroalkyl sources, thus demonstrates high potent application in life and medicinal science.

THE EVALUATION METHODS OF VELVET ANTLER AND THE DETERMINATION OF NUCLEOSIDES AND STEROID HORMONES IN DIFFERENT PARTS FROM SIKA DEER AND RED DEER

Velvet antler is an important and precious traditional Chinese animal medicine,and was used for strengthening the kidney,anti-fatigue,improving sexual function and so on.But the evaluation methods of velvet antler and the scientific evidence for the use of antler is insufficient.Materials and Vacuum freeze drier was used for dehydration of the fresh antler at-60.,6 pa for 24 h.

Qualitative and quantitative analysis of glucosinolates and nucleosides in Radix Isatidis by HPLC and liquid chromatography tandem mass spectrometry

Multi-component fingerprinting and quantitation of the glucosinolates and nucleosides in samples of Radix Isatidis have been carried out using high-performance liquid chromatography with diode-array detection and electrospray ionization tandem mass spectrometry(HPLC–DAD–ESI/MS).Five nucleosides together with one glucosinolate were identified by comparing retention times,ultraviolet spectra,mass spectra and/or empirical molecular formulae of reference compounds.Quantitation of these six compounds was carried out simultaneously by HPLC on a Phenomenex Luna C18 column using gradient elution with methanol and water and detection at 254 nm.All calibration curves were linear(r40.9994)within test ranges.Limits of detection and quantitation were 0.33 ng and 2.50 ng on column,respectively.Intra-and inter-day precision(as relative standard deviation)for all analytes was o2.19%with recoveries in the range 99.6%–101.8%at three concentration levels.The validated method was successfully applied to fingerprinting and assay of 25 batches of Radix Isatidis sourced from different geographical regions of China.The method is simple and reliable and has potential value in the quality control of Radix Isatidis.

Synthesis and Novel Properties of Alkyl Thiophosphoramidate Derivatives of Nucleosides

Novel alkyl thiophosphoramidate derivatives of nucleoside analogues (5) have been prepared by phosphochloridothioate chemistry. O Isopropyl 2′,3′ O isopropylidene uridine 5′ yl N thiophosphoryl threonine and serine methyl esters (5a and 5b) underwent the intramolecular catalyzed hydrolysis reaction.

Enzymatic synthesis of nucleosides by nucleoside phosphorylase co-expressed in Escherichia coli

Nucleoside phosphorylase is an important enzyme involved in the biosynthesis of nucleosides.In this study,purine nucleoside phosphorylase and pyrimidine nucleoside phosphorylase were co-expressed in Escherichia coli and the intact cells were used as a catalyst for the biosynthesis of nucleosides.For protein induction,lactose was used in place of isopropylβ-D-1-thiogalactopyranoside(IPTG) .When the concentration of lactose was above 0.5 mmol/L,the ability to induce protein expression was similar to that of IPTG.We determined that the reaction conditions of four bacterial strains co-expressing these genes(TUD,TAD,DUD,and DAD) were similar for the biosyntheses of 2,6-diaminopurine nucleoside and 2,6-diaminopurine deoxynucleoside.When the substrate concentration was 30 mmol/L and 0.5%of the recombinant bacterial cell volume was used as the catalyst(pH 7.5) ,a greater than 90%conversion yield was reached after a 2-h incubation at 50°C.In addition,several other nucleosides and nucleoside derivatives were efficiently synthesized using bacterial strains co-expressing these recombinant enzymes.