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Yuqi Feng - One of the best experts on this subject based on the ideXlab platform.
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comprehensive profiling of Ribonucleosides modification by affinity zirconium oxide silica composite monolithic column online solid phase microextraction mass spectrometry analysis
Journal of Chromatography A, 2016Co-Authors: Hanpeng Jiang, Bifeng Yuan, Jiemei Chu, Mengdan Lan, Ping Liu, Na Yang, Fang Zheng, Yuqi FengAbstract:More than 140 modified Ribonucleosides have been identified in RNA. Determination of endogenous modified Ribonucleosides in biological fluids may serve as non-invasive disease diagnostic strategy. However, detection of the modified Ribonucleosides in biological fluids is challenging, especially for the low abundant modified Ribonucleosides due to the serious matrix interferences of biological fluids. Here, we developed a facile preparation strategy and successfully synthesized zirconium oxide-silica (ZrO2/SiO2) composite capillary monolithic column that exhibited excellent performance for the selective enrichment of cis-diol-containing compounds. Compared with the boronate-based affinity monolith, the ZrO2/SiO2 monolith showed ∼2 orders of magnitude higher extraction capacity and can be used under physiological pH (pH 6.5-7.5). Using the prepared ZrO2/SiO2 composite monolith as the trapping column and reversed-phase C18 column as the analytical column, we further established an online solid-phase microextraction (SPME) in combination with liquid chromatography-mass spectrometry (online SPME-LC-MS/MS) analysis for the comprehensive profiling of Ribonucleosides modification in human urine. Our results showed that 68 cis-diol-containing ribosylated compounds were identified in human urine, which is, to the best of our knowledge, the highest numbers of cis-diol-containing compounds were determined in a single analysis. It is worth noting that four modified Ribonucleosides were discovered in the human urine for the first time. In addition, the quantification results from the pooled urine samples showed that compared to healthy controls, the contents of sixteen ribose conjugates in the urine of gastric cancer, eleven in esophagus cancer and seven in lymphoma increased more than two folds. Among these ribose conjugates, four ribose conjugates increased more than two folds in both gastric cancer and esophagus cancer; three ribose conjugates increased more than two folds in both gastric cancer and lymphoma; one ribose conjugate increased more than two folds in both esophagus cancer and lymphoma. The developed analytical method provides a good platform to study the modified Ribonucleosides in human body fluids.
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metal oxide based selective enrichment combined with stable isotope labeling mass spectrometry analysis for profiling of ribose conjugates
Analytical Chemistry, 2015Co-Authors: Chubo Qi, Hanpeng Jiang, Yunqing Huang, Bifeng Yuan, Yuqi FengAbstract:Some modified Ribonucleosides in biological fluids have been evaluated as cancer-related metabolites. Detection of endogenous modified Ribonucleosides in biological fluids may serve as a noninvasive cancers diagnostic method. However, determination of modified Ribonucleosides is still challenging because of their low abundance and serious matrix interferences in biological fluids. Here, we developed a novel strategy for comprehensive profiling of ribose conjugates from biological fluids using metal oxide-based dispersive solid-phase extraction (DSPE) followed with in vitro stable isotope labeling and double neutral loss scan-mass spectrometry analysis (DSPE-SIL-LC-DNLS-MS). Cerium dioxide (CeO2) was used to selectively recognize and capture ribose conjugates from complex biological samples under basic environment. The enriched ribose conjugates were subsequently labeled with a pair of isotope labeling reagents (acetone and acetone-d6). The glucosidic bond of acetone labeled ribose conjugates is readily ru...
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TiO2-based solid phase extraction strategy for highly effective elimination of normal Ribonucleosides before detection of 2'-deoxynucleosides/low-abundance 2'-O-modified Ribonucleosides.
Analytical Chemistry, 2013Co-Authors: Shao-ting Wang, Bifeng Yuan, Wei Lu, Wei Huang, Yuqi FengAbstract:A novel TiO2-based SPE strategy was developed for eliminating normal Ribonucleosides before mass spectrometry (MS) analysis of 2′-deoxynucleosides and 2′-O-modified Ribonucleosides. The chromatographic research for the retention behavior of Ribonucleosides and 2′-deoxynucleosides on TiO2 materials was investigated using TiO2 separation column. The results indicated a specific affinity interaction mechanism between TiO2 and cis-diol-containing Ribonucleosides, and the interaction was proved effective even under a wide range of pH conditions and salt concentrations. Benefiting from these features, a TiO2-based solid phase extraction (SPE) method was developed for highly efficient elimination of RNA contamination from genomic DNA. Compared with the widely used enzymatic digestion method, the proposed TiO2-based SPE method showed much more efficiency for the removal of RNA as well as provided high recoveries for the 2′-deoxynucleosides. In addition, the sample processing time is dramatically shortened using t...
Michal Hocek - One of the best experts on this subject based on the ideXlab platform.
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Synthesis and antiviral activity of 4,6-disubstituted pyrimido[4,5-b]indole Ribonucleosides
Bioorganic & medicinal chemistry, 2012Co-Authors: Michal Tichý, Radek Pohl, Yen Liang Chen, Fumiaki Yokokawa, Pei Yong Shi, Michal HocekAbstract:A series of new pyrimido[4,5-b]indole Ribonucleosides bearing phenyl or hetaryl group at position 4 has been prepared by selective Pd-catalyzed cross-coupling reactions of the corresponding protected 4,6-dichloropyrimido[4,5-b]indole ribonucleoside with (het)arylboronic acids or stannanes followed by deprotection. Further cross-couplings under harsher conditions and employing X-Phos ligand proceeded at the position 6 leading to 4,6-disubstituted pyrimido[4,5-b]indole Ribonucleosides. Some of these compounds displayed antiviral activity against Dengue virus.
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Synthesis of Substituted Benzyl Homo‐C‐Ribonucleosides and ‐Nucleotides as Carba Analogues of Phosphoribosylanthranilate
European Journal of Organic Chemistry, 2012Co-Authors: Tomáš Kubelka, Lenka Poštová Slavětínská, Michal HocekAbstract:New 2-substituted benzyl C-Ribonucleosides and -nucleotides were designed as carba analogues of phosphoribosylanthranilate, a key intermediate in tryptophan biosynthesis. The synthesis was based on the preparation of TBS-protected 2-bromobenzyl C-ribonucleoside 4a by addition of (2-bromobenzyl)magnesium bromide to ribonolactone followed by reduction and subsequent functional group transformations. Pd-catalyzed hydrogenation, cross-couplings, amination or hydroxylation, as well as lithiation followed by reaction with CO2 and amidations, gave a large series of 2-alkyl-, 2-(het)aryl, 2-amino, 2-hydroxy, 2-carboxy and 2-carbamoyl derivatives that were deprotected to afford free homo-C-Ribonucleosides. Some of the title nucleosides were converted to 5′-O-phosphates.
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phosphoramidate pronucleotides of cytostatic 6 aryl 7 deazapurine Ribonucleosides
Bioorganic & Medicinal Chemistry, 2011Co-Authors: Pavla Perlikova, Radek Pohl, Ivan Votruba, Robert Shih, Gabriel Birkus, Tomas Cihlař, Michal HocekAbstract:A series of O-phenyl methyl-, ethyl- and benzylalanyl phosphoramidate pronucleotides derived from cytostatic 6-aryl-7-deazapurine Ribonucleosides were prepared by the cross-coupling reactions of the 2',3'-isopropylidene protected 6-chloro-7-deazapurine ribonucleoside phosphoramidates with (het)arylboronic acids or -stannanes followed by deprotection. Most of the prepared prodrugs exerted in vitro cytostatic effects against both solid tumor and lymphoid cancer cells within low micromolar range of concentrations. These activities were in general weaker or comparable to the activities of the parent nucleosides. Additional testing of selected prodrugs suggests that the lack of activity improvement over parent nucleosides is not due to the lack of permeability or inefficient catabolism of alanyl-ester by intracellular hydrolases. More likely, active efflux of prodrugs may play a role in their weak cytotoxic activity.
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Synthesis of benzamide-C-Ribonucleosides by Pd-catalyzed aminocarbonylations
Tetrahedron, 2009Co-Authors: Martin Štefko, Radek Pohl, Michal HocekAbstract:Abstract A novel modular, efficient and practical methodology for preparation of p - and m -substituted benzamide- C -Ribonucleosides was developed. Reaction of TBS-protected 3- and 4-bromophenyl- C -Ribonucleosides 1 and 4 with various primary and secondary amines or NH 4 Cl under atmospheric pressure of carbon monoxide and in the presence of Pd(OAc) 2 and Xantphos lead to the corresponding amides 2a – j and 5a – j in high yields. Subsequent deprotection of silylated nucleosides by Et 3 N·3HF or TFA afforded a series of free C -Ribonucleosides 3a – j or 6a – j in excellent yields (20 examples).
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Cytostatic and Antiviral 6-Arylpurine Ribonucleosides IX. Synthesis and Evaluation of 6-Substituted 3-Deazapurine Ribonucleosides
Collection of Czechoslovak Chemical Communications, 2008Co-Authors: Petr Nauš, Martin Kuchař, Michal HocekAbstract:A series of 3-deazapurine Ribonucleosides 5a–5l bearing diverse C-substituents (alkyl, aryl and heteroaryl) in the position 6 were prepared by Pd-catalyzed cross-coupling reactions of either free 6-chloro-3-deazapurine ribonucleoside 4 or its acetyl protected congener 3 followed by deprotection. An improved synthesis of the starting 4-chloro-1-(2,3,5-tri-O-acetylβ-D-ribofuranosyl)-1H-imidazo[4,5-c]pyridine (3) was developed by the application of Vorbruggen glycosylation of silylated nucleobase with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose (2). None of compounds 5a–5l showed any considerable cytostatic or antiviral activity.
Bifeng Yuan - One of the best experts on this subject based on the ideXlab platform.
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comprehensive profiling of Ribonucleosides modification by affinity zirconium oxide silica composite monolithic column online solid phase microextraction mass spectrometry analysis
Journal of Chromatography A, 2016Co-Authors: Hanpeng Jiang, Bifeng Yuan, Jiemei Chu, Mengdan Lan, Ping Liu, Na Yang, Fang Zheng, Yuqi FengAbstract:More than 140 modified Ribonucleosides have been identified in RNA. Determination of endogenous modified Ribonucleosides in biological fluids may serve as non-invasive disease diagnostic strategy. However, detection of the modified Ribonucleosides in biological fluids is challenging, especially for the low abundant modified Ribonucleosides due to the serious matrix interferences of biological fluids. Here, we developed a facile preparation strategy and successfully synthesized zirconium oxide-silica (ZrO2/SiO2) composite capillary monolithic column that exhibited excellent performance for the selective enrichment of cis-diol-containing compounds. Compared with the boronate-based affinity monolith, the ZrO2/SiO2 monolith showed ∼2 orders of magnitude higher extraction capacity and can be used under physiological pH (pH 6.5-7.5). Using the prepared ZrO2/SiO2 composite monolith as the trapping column and reversed-phase C18 column as the analytical column, we further established an online solid-phase microextraction (SPME) in combination with liquid chromatography-mass spectrometry (online SPME-LC-MS/MS) analysis for the comprehensive profiling of Ribonucleosides modification in human urine. Our results showed that 68 cis-diol-containing ribosylated compounds were identified in human urine, which is, to the best of our knowledge, the highest numbers of cis-diol-containing compounds were determined in a single analysis. It is worth noting that four modified Ribonucleosides were discovered in the human urine for the first time. In addition, the quantification results from the pooled urine samples showed that compared to healthy controls, the contents of sixteen ribose conjugates in the urine of gastric cancer, eleven in esophagus cancer and seven in lymphoma increased more than two folds. Among these ribose conjugates, four ribose conjugates increased more than two folds in both gastric cancer and esophagus cancer; three ribose conjugates increased more than two folds in both gastric cancer and lymphoma; one ribose conjugate increased more than two folds in both esophagus cancer and lymphoma. The developed analytical method provides a good platform to study the modified Ribonucleosides in human body fluids.
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metal oxide based selective enrichment combined with stable isotope labeling mass spectrometry analysis for profiling of ribose conjugates
Analytical Chemistry, 2015Co-Authors: Chubo Qi, Hanpeng Jiang, Yunqing Huang, Bifeng Yuan, Yuqi FengAbstract:Some modified Ribonucleosides in biological fluids have been evaluated as cancer-related metabolites. Detection of endogenous modified Ribonucleosides in biological fluids may serve as a noninvasive cancers diagnostic method. However, determination of modified Ribonucleosides is still challenging because of their low abundance and serious matrix interferences in biological fluids. Here, we developed a novel strategy for comprehensive profiling of ribose conjugates from biological fluids using metal oxide-based dispersive solid-phase extraction (DSPE) followed with in vitro stable isotope labeling and double neutral loss scan-mass spectrometry analysis (DSPE-SIL-LC-DNLS-MS). Cerium dioxide (CeO2) was used to selectively recognize and capture ribose conjugates from complex biological samples under basic environment. The enriched ribose conjugates were subsequently labeled with a pair of isotope labeling reagents (acetone and acetone-d6). The glucosidic bond of acetone labeled ribose conjugates is readily ru...
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TiO2-based solid phase extraction strategy for highly effective elimination of normal Ribonucleosides before detection of 2'-deoxynucleosides/low-abundance 2'-O-modified Ribonucleosides.
Analytical Chemistry, 2013Co-Authors: Shao-ting Wang, Bifeng Yuan, Wei Lu, Wei Huang, Yuqi FengAbstract:A novel TiO2-based SPE strategy was developed for eliminating normal Ribonucleosides before mass spectrometry (MS) analysis of 2′-deoxynucleosides and 2′-O-modified Ribonucleosides. The chromatographic research for the retention behavior of Ribonucleosides and 2′-deoxynucleosides on TiO2 materials was investigated using TiO2 separation column. The results indicated a specific affinity interaction mechanism between TiO2 and cis-diol-containing Ribonucleosides, and the interaction was proved effective even under a wide range of pH conditions and salt concentrations. Benefiting from these features, a TiO2-based solid phase extraction (SPE) method was developed for highly efficient elimination of RNA contamination from genomic DNA. Compared with the widely used enzymatic digestion method, the proposed TiO2-based SPE method showed much more efficiency for the removal of RNA as well as provided high recoveries for the 2′-deoxynucleosides. In addition, the sample processing time is dramatically shortened using t...
Hideo Yoshizumi - One of the best experts on this subject based on the ideXlab platform.
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RNA metabolism in uremic patients: Accumulation of modified Ribonucleosides in uremic serum
Kidney International, 1998Co-Authors: Toshimitsu Niwa, Naohito Takeda, Hideo YoshizumiAbstract:RNA metabolism in uremic patients: Accumulation of modified Ribonucleosides in uremic serum. To determine the metabolism of ribonucleic acid (RNA) in uremia, serum and urine levels of Ribonucleosides in uremic patients were analyzed using reversed-phase high-performance liquid chromatography. The serum levels of xanthosine and all modified Ribonucleosides were increased in undialyzed patients with chronic renal failure (CRF), and patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). The serum level of pseudouridine was markedly increased in all the uremic patients especially CAPD patients (32 times higher than normal). By contrast, the serum level of adenosine did not show any significant change in the uremic patients. Interestingly, the serum and urine levels of inosine were significantly decreased in all the uremic patients, suggesting that the production of inosine is decreased in uremic patients. The serum level of uridine was significantly elevated only in the HD patients. The serum levels of all Ribonucleosides except inosine and uridine decreased significantly after HD. The urinary excretion of inosine, 1-methyladenosine, 1-methylguanosine, N 2 ,N 2 -dimethylguanosine and N 4 -acetylcytidine was significantly decreased in the CRF patients, leading to the accumulation of these modified Ribonucleosides in the uremic serum. CAPD patients showed markedly increased serum levels of modified Ribonucleosides such as pseudouridine, 1-methylinosine, and N 2 ,N 2 -dimethylguanosine and N 4 -acetylcytidine as compared with the HD patients. These results demonstrate that there was an altered metabolism of RNA in uremic patients with marked accumulation of modified Ribonucleosides.
Peter C Dedon - One of the best experts on this subject based on the ideXlab platform.
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Quantitative analysis of ribonucleoside modifications in tRNA by HPLC-coupled mass spectrometry
Nature Protocols, 2014Co-Authors: Dan Su, Clement T Y Chan, Brandon S Russell, Thomas J Begley, Chen Gu, Megan E. Mcbee, Yok Hian Chionh, I. Ramesh Babu, Peter C DedonAbstract:Post-transcriptional modification of RNA is an important determinant of RNA quality control, translational efficiency, RNA-protein interactions and stress response. This is illustrated by the observation of toxicant-specific changes in the spectrum of tRNA modifications in a stress-response mechanism involving selective translation of codon-biased mRNA for crucial proteins. To facilitate systems-level studies of RNA modifications, we developed a liquid chromatography–mass spectrometry (LC-MS) technique for the quantitative analysis of modified Ribonucleosides in tRNA. The protocol includes tRNA purification by HPLC, enzymatic hydrolysis, reversed-phase HPLC resolution of the Ribonucleosides, and identification and quantification of individual Ribonucleosides by LC-MS via dynamic multiple reaction monitoring (DMRM). In this approach, the relative proportions of modified Ribonucleosides are quantified in several micrograms of tRNA in a 15-min LC-MS run. This protocol can be modified to analyze other types of RNA by modifying the steps for RNA purification as appropriate. By comparison, traditional methods for detecting modified Ribonucleosides are labor- and time-intensive, they require larger RNA quantities, they are modification-specific or require radioactive labeling.
