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61.
62.
Jane A. Grasby Clare E. Pritchard Michael J. Gait 《Journal of Chemical Sciences》1994,106(5):1003-1022
The study of RNA structure and function has been considerably aided by the development of methods for the chemical synthesis
of oligoribonucleotides into which have been incorporated modified nucleosides carrying site-specific alterations. Such modifications
are designed to eliminate or alter individual functional groups in the RNA which potentially can take part in hydrogen-bonding
or other non-covalent interactions. Comparison of the properties of the modified RNA with unmodified RNA models allows conclusions
to be drawn concerning the importance or otherwise of specific functional groups within the RNA. The methods have been applied
to studies of RNA structure, RNA catalysis, and interactions of RNA with proteins. 相似文献
63.
Cheng Qu Hui Yan Shao‐Qing Zhu Yi‐Yun Qian Gui‐Sheng Zhou Sheng Guo Zhen‐Hua Zhu Sen Zhang Da‐Wei Qian Jin‐Ao Duan 《Journal of separation science》2019,42(6):1122-1132
A rapid and sensitive ultra high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry method was established and employed to determine 21 nucleosides, nucleobases, and amino acids in 60 samples from different parts of Angelicae Sinensis Radix. The established methods were validated by good linearity (r2 > 0.9937), limits of detection (0.12–77.75 ng/mL), limits of quantitation (0.31–272.13 ng/mL), intra‐ and interday precisions (RSD ≤ 4.84%, RSD ≤ 6.26%), stability (RSD ≤ 5.92%), repeatability (RSD ≤ 7.14%), recovery (91.4–103.4%), and matrix effects (0.92–1.03). Chemical comparative analysis revealed that the content of total analytes in four parts of Angelicae Sinensis Radix were different, and exhibited the order: Head (14.89 mg/g) > Body (10.15 mg/g) > All (8.22 mg/g) > Tail (6.23 mg/g). Principal component analysis showed that the samples could be classified into four groups in accord with four different parts of Angelicae Sinensis Radix. The results could provide a scientific basis and reference for the quality control of Angelicae Sinensis Radix, and may be conducive to further research on the pharmacological activities of Angelicae Sinensis Radix. 相似文献
64.
Ruijuan Liu Fang Zhao Jingyao Wei Pei Yu Ji Zhang Yueqin Wang Zeyun Li Jiali Zhang Xiaojian Zhang Xin Tian 《Journal of separation science》2019,42(16):2668-2678
Ribonucleic acid N6‐methyladenosine methylation plays an important role in a variety of biological processes and diseases. Acetaminophen‐induced hepatotoxicity is one of the major challenges faced by clinicians. To date, the link between N6‐methyladenosine and acetaminophen‐induced hepatotoxicity has not been studied. In this study, a simple ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of five nucleosides (adenosine, uridine, cytidine, guanosine, and N6‐methyladenosine) in messenger ribonucleic acid. After enzymatic digestion of messenger ribonucleic acid, the nucleosides sample was separated on an Acquity UPLC column with gradient elution using methanol and 0.02% formic acid water, and detected by a Qtrap 4500 mass spectrometer with an electrospray ionization mode. The method was validated over the concentration ranges of 4–800 ng/mL for adenosine, uridine, cytidine, and guanosine and 0.1–20 ng/mL for N6‐methyladenosine. It was successfully applied to the determination of N6‐methyladenosine levels in liver messenger ribonucleic acid in an acetaminophen‐induced hepatotoxicity mouse model and a control group. This study offers a method for the determination of nucleoside contents in epigenetic studies and constitutes the first step toward the investigation of ribonucleic acid methylation in acetaminophen‐induced hepatotoxicity, which will facilitate the elucidation of its mechanism. 相似文献
65.
Paul T. Ludford III Shenghua Yang Marcela S. Bucardo Prof. Yitzhak Tor 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(13):e202104472
A new fluorescent ribonucleoside alphabet (mthN) consisting of pyrimidine and purine analogues, all derived from methylthieno[3,4-d]pyrimidine as the heterocyclic core, is described. Large bathochromic shifts and high microenvironmental susceptibility of their emission relative to previous alphabets derived from thieno[3,4-d]pyrimidine (thN) and isothiazole[4,3-d]pyrimidine (tzN) scaffolds are observed. Subjecting the purine analogues to adenosine deaminase, guanine deaminase and T7 RNA polymerase indicate that, while varying, all but one enzyme tolerate the corresponding mthN/mthNTP substrates. The robust emission quantum yields, high photophysical responsiveness and enzymatic accommodation suggest that the mthN alphabet is a biophysically viable tool and can be used to probe the tolerance of nucleoside/tide-processing enzymes to structural perturbations of their substrates. 相似文献
66.
Mathias B. Danielsen Dr. Chenguang Lou Jolanta Lisowiec-Wachnicka Prof. Anna Pasternak Per T. Jørgensen Prof. Jesper Wengel 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(6):1368-1379
Off-target effects remain a significant challenge in the therapeutic use of gapmer antisense oligonucleotides (AONs). Over the years various modifications have been synthesized and incorporated into AONs, however, precise control of RNase H-induced cleavage and target sequence selectivity has yet to be realized. Herein, the synthesis of the uracil and cytosine derivatives of a novel class of 2′-deoxy-2′-fluoro-3′-C-hydroxymethyl-β-d -lyxo-configured nucleotides has been accomplished and the target molecules have been incorporated into AONs. Experiments on exonuclease degradation showed improved nucleolytic stability relative to the unmodified control. Upon the introduction of one or two of the novel 2′-fluoro-3′-C-hydroxymethyl nucleotides as modifications in the gap region of a gapmer AON was associated with efficient RNase H-mediated cleavage of the RNA strand of the corresponding AON:RNA duplex. Notably, a tailored single cleavage event could be engineered depending on the positioning of a single modification. The effect of single mismatched base pairs was scanned along the full gap region demonstrating that the modification enables a remarkable specificity of RNase H cleavage. A cell-based model system was used to demonstrate the potential of gapmer AONs containing the novel modification to mediate gene silencing. 相似文献
67.
Mingwu Yu Xiguang Liu Qingsong Jiang Hongguang Du 《Phosphorus, sulfur, and silicon and the related elements》2018,193(7):451-458
An expeditious and convenient method to synthesize 9-allenylpurines via cesium carbonate catalyzed isomerization of 9-alkynylpurines has been successfully developed. The reactions proceeded rapidly under the base conditions and formed the desired products in good to excellent yields. The method was suitable with a broad substrate scope and proceeded well even on a multgram-scale. The obtained 9-allenylpurines were successfully applied to prepare various potential bioactive 9-acyclic nucleosides with high regioselectivity promoted by AgNO3. 相似文献
68.
69.
70.
Georgii V. Bobkov Sergey N. Mikhailov Arthur Van Aerschot Piet Herdewijn 《Tetrahedron》2008,64(27):6238-6251
A simple and efficient method for the preparation of eight phosphoramidite building blocks for incorporation of 2′-O-(2-aminoethoxymethyl)ribonucleosides and 2′-O-(3-aminopropoxymethyl)ribonucleosides into synthetic oligonucleotides has been developed. The synthetic routes are maximally convergent and provide sufficient amounts of phosphoramidites for several solid-phase synthesis coupling reactions. Using acyclic derivatives 17a,b the overall yields of phosphoramidites 2 and 3 were increased up to 50% for pyrimidine nucleosides and up to 30% for purine derivatives with substantial decrease of total reaction steps. The 2′-O-substituent was found to be stable during oligonucleotide synthesis. The resulting oligonucleotides are of particular interest for post-synthetic functionalization and conjugation. 相似文献