50-89-5Relevant articles and documents
An Improved Approach for Practical Synthesis of 5-Hydroxymethyl-2′-deoxycytidine (5hmdC) Phosphoramidite and Triphosphate
Chen, Zhen-Zhen,Chi, Mei,Dong, Ying-Ying,Pu, Shou-Zhi,Sun, Qi,Yang, Dong-Zhao
, (2022/01/31)
5-Hydroxymethyl-2′-deoxycytidine (5hmdC) phosphoramidite and triphosphate are important building blocks in 5hmdC-containing DNA synthesis for epigenetic studies. However, efficient and practical methods for the synthesis of these compounds are
Biochemical characterization of a recombinant acid phosphatase from Acinetobacter baumannii
Smiley-Moreno, Elizabeth,Smith, Douglas,Yu, Jieh-Juen,Cao, Phuong,Arulanandam, Bernard P.,Chambers, James P.
, (2021/06/09)
Genomic sequence analysis of Acinetobacter baumannii revealed the presence of a putative Acid Phosphatase (AcpA; EC 3.1.3.2). A plasmid construct was made, and recombinant protein (rAcpA) was expressed in E. coli. PAGE analysis (carried out under denaturing/ reducing conditions) of nickel-affinity purified protein revealed the presence of a nearhomogeneous band of approximately 37 kDa. The identity of the 37 kDa species was verified as rAcpA by proteomic analysis with a molecular mass of 34.6 kDa from the deduced sequence. The dependence of substrate hydrolysis on pH was broad with an optimum observed at 6.0. Kinetic analysis revealed relatively high affinity for PNPP (Km = 90 μM) with Vmax, kcat, and Kcat/Km values of 19.2 pmoles s-1, 4.80 s-1(calculated on the basis of 37 kDa), and 5.30 × 104 M-1s-1, respectively. Sensitivity to a variety of reagents, i.e., detergents, reducing, and chelating agents as well as classic acid phosphatase inhibitors was examined in addition to assessment of hydrolysis of a number of phosphorylated compounds. Removal of phosphate from different phosphorylated compounds is supportive of broad, i.e., 'nonspecific' substrate specificity; although, the enzyme appears to prefer phosphotyrosine and/or peptides containing phosphotyrosine in comparison to serine and threonine. Examination of the primary sequence indicated the absence of signature sequences characteristic of Type A, B, and C nonspecific bacterial acid phosphatases.
Meteorite-catalyzed intermoleculartrans-glycosylation produces nucleosides under proton beam irradiation
Bizzarri, Bruno Mattia,Fanelli, Angelica,Kapralov, Michail,Krasavin, Eugene,Saladino, Raffaele
, p. 19258 - 19264 (2021/06/03)
Di-glycosylated adenines act as glycosyl donors in the intermoleculartrans-glycosylation of pyrimidine nucleobases under proton beam irradiation conditions. Formamide and chondrite meteorite NWA 1465 increased the yield and the selectivity of the reaction
SYNTHESIS AND IMPROVEMENT OF A NUCLEOSIDE ANALOGUE AS AN ANTI-CANCER AND ANTI-VIRAL DRUG
-
, (2021/05/29)
The invention is a drug for anticancer and antiviral therapy, comprising a nucleoside analogue (7) comprising a furan ring irreversibly bound to the RNA/DNA synthesis chain by phosphodiester bonds and having SP3 hybridization, and folic acid (A) bound to the nucleoside analogue (7) comprising furan ring. The synthesis method of the said nucleoside analogue is also contained within the scope of the invention. In this work, a nucleoside-analogue was transformed after converting the furan-ring hybridization from Sp2 to Sp3 to make it more selectivity with different enzymes and linking it via site 5 with the effective folic acid towards entering the substances inside the cells and to become the final compound possessing anti-cancer and anti- virus properties after controlling the replication and reproduction process in DNA.
RETRACTED ARTICLE: Divergent synthesis of 5-substituted pyrimidine 2′-deoxynucleosides and their incorporation into oligodeoxynucleotides for the survey of uracil DNA glycosylases
Tran, Ai,Zheng, Song,White, Dawanna S.,Curry, Alyson M.,Cen, Yana
, p. 11818 - 11826 (2020/11/18)
Recent studies have indicated that 5-methylcytosine (5mC) residues in DNA can be oxidized and potentially deaminated to the corresponding thymine analogs. Some of these oxidative DNA damages have been implicated as new epigenetic markers that could have profound influences on chromatin function as well as disease pathology. In response to oxidative damage, the cells have a complex network of repair systems that recognize, remove and rebuild the lesions. However, how the modified nucleobases are detected and repaired remains elusive, largely due to the limited availability of synthetic oligodeoxynucleotides (ODNs) containing these novel DNA modifications. A concise and divergent synthetic strategy to 5mC derivatives has been developed. These derivatives were further elaborated to the corresponding phosphoramidites to enable the site-specific incorporation of modified nucleobases into ODNs using standard solid-phase DNA synthesis. The synthetic methodology, along with the panel of ODNs, is of great value to investigate the biological functions of epigenetically important nucleobases, and to elucidate the diversity in chemical lesion repair.
RETRACTED ARTICLE: Convenient synthesis of pyrimidine 2′-deoxyribonucleoside monophosphates with important epigenetic marks at the 5-position
Zheng, Song,Tran, Ai,Curry, Alyson M.,White, Dawanna S.,Cen, Yana
, p. 5164 - 5173 (2020/07/23)
Methyl groups of thymine and 5-methylcytosine (5mC) bases in DNA undergo endogenous oxidation damage. Additionally, 5mC residues can be enzymatically deaminated or oxidized through either genetic alterations or the newly identified epigenetic reprogramming pathway. Several methods have been developed to measure the formation of modified DNA nucleobases including 32P-postlabeling. However, the postlabeling method is often limited by the absence of authentic chemical standards. The synthesis of monophosphate standards of nucleotide oxidation products is complicated by the presence of additional functional groups on the modified bases that require complex protection and deprotection strategies. Due to the emerging interest in the pyrimidine oxidation products, the corresponding protected 3′-phosphoramidites needed for solid-phase oligonucleotide synthesis have been reported, and several are commercially available. We report here an efficient synthesis of 3′-monophosphates from 3′-phosphoramidites and the subsequent enzymatic conversion of 3′-monophosphates to the corresponding 5′-monophosphates using commercially available enzymes. This journal is
Spacer-Mediated Control of Coumarin Uncaging for Photocaged Thymidine
Baker, James R.,Cannon, Jayme,Choi, Seok Ki,Krummel, Matthew F.,Tang, Shengzhuang,Yang, Kelly
, (2020/02/22)
Despite its importance in the design of photocaged molecules, less attention is focused on linker chemistry than the cage itself. Here, we describe unique uncaging properties displayed by two coumarin-caged thymidine compounds, each conjugated with (2) or without (1) an extended, self-immolative spacer. Photolysis of 1 using long-wavelength UVA (365 nm) or visible (420, 455 nm) light led to the release of free thymidine along with the competitive generation of a thymidine-bearing recombination product. The occurrence of this undesired side reaction, which is previously unreported, was not present with the photolysis of 2, which released thymidine exclusively with higher quantum efficiency. We propose that the spatial separation between the cage and the substrate molecule conferred by the extended linker can play a critical role in circumventing this unproductive reaction. This report reinforces the importance of linker selection in the design of coumarin-caged oligonucleosides and other conjugates.
Method for preparing beta-thymidine by adopting solid acid catalysis
-
Paragraph 0016-0017, (2020/07/15)
The invention relates to a method for preparing beta-thymidine by adopting solid acid catalysis. The method includes the following steps: the toluene feed liquid of intermediate bromide is obtained by5-methyluridine and [1] under the action of a solid acid and a phase transfer catalyst; and reduction reaction is performed on the toluene feed liquid of the intermediate bromide by using a palladium-carbon catalyst under characteristic environments, and the beta-thymidine is generated through post-treatment crystallization. The method is controllable in reaction condition, high in yield, low incost and suitable for industrial production, and has industrial application value.
Thermodynamic Reaction Control of Nucleoside Phosphorolysis
Kaspar, Felix,Giessmann, Robert T.,Neubauer, Peter,Wagner, Anke,Gimpel, Matthias
supporting information, p. 867 - 876 (2020/01/24)
Nucleoside analogs represent a class of important drugs for cancer and antiviral treatments. Nucleoside phosphorylases (NPases) catalyze the phosphorolysis of nucleosides and are widely employed for the synthesis of pentose-1-phosphates and nucleoside analogs, which are difficult to access via conventional synthetic methods. However, for the vast majority of nucleosides, it has been observed that either no or incomplete conversion of the starting materials is achieved in NPase-catalyzed reactions. For some substrates, it has been shown that these reactions are reversible equilibrium reactions that adhere to the law of mass action. In this contribution, we broadly demonstrate that nucleoside phosphorolysis is a thermodynamically controlled endothermic reaction that proceeds to a reaction equilibrium dictated by the substrate-specific equilibrium constant of phosphorolysis, irrespective of the type or amount of NPase used, as shown by several examples. Furthermore, we explored the temperature-dependency of nucleoside phosphorolysis equilibrium states and provide the apparent transformed reaction enthalpy and apparent transformed reaction entropy for 24 nucleosides, confirming that these conversions are thermodynamically controlled endothermic reactions. This data allows calculation of the Gibbs free energy and, consequently, the equilibrium constant of phosphorolysis at any given reaction temperature. Overall, our investigations revealed that pyrimidine nucleosides are generally more susceptible to phosphorolysis than purine nucleosides. The data disclosed in this work allow the accurate prediction of phosphorolysis or transglycosylation yields for a range of pyrimidine and purine nucleosides and thus serve to empower further research in the field of nucleoside biocatalysis. (Figure presented.).
Tuning the stability of alkoxyisopropyl protection groups
Liang, Zehong,Koivikko, Henna,Oivanen, Mikko,Heinonen, Petri
supporting information, p. 746 - 751 (2019/04/17)
Five different 2-alkoxypropan-2-yl groups are introduced as acid-labile protecting groups for the 5’- and 3’-hydroxy groups of a 2’-deoxynucleoside. All studied protecting groups were readily introduced with good to excellent yields using the appropriate enol ether as a reagent and 0.5 to 1 mol % p-toluenesulfonic acid as a catalyst. The protected compounds could be purified by silica gel column chromatography without degradation. The compatibility of these protecting groups in parallel use with benzoyl and silyl groups was verified. The stabilities of the different alkoxy acetal protecting groups were compared by following the kinetics of their hydrolysis at 25.0 °C in buffered solutions through an HPLC method. In the pH range 4.94 to 6.82 the hydrolysis reactions are of first order in the hydronium ion. The rate of hydrolysis correlates with the electron-donating or electron-withdrawing ability of the corresponding alkoxy group. The studied 2-alkoxypropan-2-yl groups and the relative rate constants for their cleavage from the 5’-hydroxy group of 2’-deoxythymidine were: cyclohexyloxy (krel = 7.7), isopropoxy (7.4), methoxy (1), benzyloxy (0.6) and 2,2,2-trifluoroethyloxy (0.04). The attachment of the same groups to the 3’-hydroxy group are from 1.3 to 1.9-fold more stable. The most reactive of these acetone-based acetal groups are faster removed than a dimethoxytrityl group, and they are easier to cleave completely in solution. The structural variation allows steering of the stability and lipophilicity of the compounds in some range.
