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Modified Nucleosides (modified + nucleoside)

Distribution by Scientific Domains

Chemistry	100%

Selected Abstracts

Analysis of urinary nucleosides as helper tumor markers in hepatocellular carcinoma diagnosis

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 11 2009
Long-Bin Jeng
Hepatocellular carcinoma (HCC) is a common neoplasm in Taiwan, for which early diagnosis is difficult and the prognosis is usually poor. HCC is usually diagnosed by abdominal sonography and serum alpha-fetoprotein (AFP) detection. Modified nucleosides, regarded as indicators for the whole-body turnover of RNAs, are excreted in abnormal amounts in the urine of patients with malignancies and can serve as tumor markers. We analyzed the excretion patterns of urinary nucleosides from 25 HCC patients and 20 healthy volunteers by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) under optimized conditions. The HPLC/ESI-MS/MS approach with selective reaction monitoring (SRM) allowed for the sensitive determination of nucleosides in human urine samples. The mean levels of the urinary nucleosides adenosine, cytidine, and inosine were significantly higher in HCC patients than healthy volunteers (average of 1.78-, 2.26-, and 1.47-fold, respectively). However, the mean levels of urinary 1-methyladenosine, 3-methylcytidine, uridine, and 2,-deoxyguanosine were not significantly different. Combined with the determination of serum AFP levels, the higher levels of urinary adenosine, cytidine, and inosine may be additional diagnosis markers for HCC in Taiwanese patients. Copyright © 2009 John Wiley & Sons, Ltd. [source]

A new chemical method of synthesis of modified nucleoside [32P]phosphates

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2008
D. V. Yanvarev
Abstract A simple method of chemical phosphorylation for modified nucleosides with [32P]orthophosphoric acid in the presence of BrCN is described. The yields of 5,-[32P]nucleoside monophosphates achieved are 50,65% at nominal specific radioactivities of ca. 1000,Ci/mmol. The mechanism of phosphorylation in the presence of heterocyclic amines is studied. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Proton affinity ladder for uridine and analogs: influence of the hydroxyl group on the sugar ring conformation

JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2005
S. Mezzache
Abstract A ladder of relative proton affinities (PA) for a series of modified uridines (e.g. araU, ddU, 5BrU, 5BrdU and 5IU) was established from competitive dissociations of proton-bound heterodimers using Cooks and co-workers' kinetic method. The studied heterodimers are constituted of a modified nucleoside and either an amino acid or a nucleoside with known PA value. These non-covalent heterodimers were prepared under electrospray conditions to be selected and dissociated into the ion-trap analyzer. These results allowed our PA ladder of uridine and deoxyuridine analogs substituted at the C-5 position in the uracil ring to be extended. From this scale, it was showed that the substitution of hydrogen atom at the C-2, position in the sugar ring by a hydroxyl group involves a decrease of about 7 kJ mol,1. The experimental values for U, 5MeU, dU, 5MedU, ddU and araU are consistent with those obtained by DFT calculations (B3P86/6,31+G*//B3LYP/6,31G*). Several neutral and protonated conformations of these compounds were considered, in particular the ring conformation of furanose and the orientation of the base with respect to the sugar ring. These calculated results showed the influence of sugar substituent on the conformation of the neutral form of theses nucleosides. However, the most stable protonated structure is the same for all the studied nucleosides except for araU, where the position of the anti 2,-OH group imposes a specific conformation. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Oligonucleotide N3,,P5, Phosphoramidates and Thio -Phoshoramidates as Potential Therapeutic Agents

CHEMISTRY & BIODIVERSITY, Issue 3 2010
Sergei
Abstract Nucleic acids analogues, i.e., oligonucleotide N3,,P5, phosphoramidates and N3,,P5, thio -phosphoramidates, containing 3,-amino-3,-deoxy nucleosides with various 2,-substituents were synthesized and extensively studied. These compounds resist nuclease hydrolysis and form stable duplexes with complementary native phosphodiester DNA and, particularly, RNA strands. An increase in duplexes' melting temperature, ,Tm, relative to their phosphodiester counterparts, reaches 2.2,4.0° per modified nucleoside. 2,-OH- (RNA-like), 2,- O -Me-, and 2,- ribo -F-nucleoside substitutions result in the highest degree of duplex stabilization. Moreover, under close to physiological salt and pH conditions, the 2,-deoxy- and 2,-fluoro-phosphoramidate compounds form extremely stable triple-stranded complexes with either single- or double-stranded phosphodiester DNA oligonucleotides. Melting temperature, Tm, of these triplexes exceeds Tm values for the isosequential phosphodiester counterparts by up to 35°. 2,-Deoxy-N3,,P5, phosphoramidates adopt RNA-like C3,- endo or N -type nucleoside sugar-ring conformations and hence can be used as stable RNA mimetics. Duplexes formed by 2,-deoxy phosphoramidates with complementary RNA strands are not substrates for RNase H-mediated cleavage in vitro. Oligonucleotide phosphoramidates and especially thio -phosphoramidates conjugated with lipid groups are cell-permeable and demonstrate high biological target specific activity in vitro. In vivo, these compounds show good bioavailability and efficient biodistribution to all major organs, while exerting acceptable toxicity at therapeutically relevant doses. Short oligonucleotide N3,,P5, thio -phosphoramidate conjugated to 5,-palmitoyl group, designated as GRN163L (Imetelstat), was recently introduced as a potent human telomerase inhibitor. GRN163L is not an antisense agent; it is a direct competitive inhibitor of human telomerase, which directly binds to the active site of the enzyme and thus inhibits its activity. This compound is currently in multiple Phase-I and Phase-I/II clinical trials as potential broad-spectrum anticancer agent. [source]

A Versatile Synthesis of 5,-Functionalized Nucleosides Through Regioselective Enzymatic Hydrolysis of Their Peracetylated Precursors

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 12 2009
Teodora Bavaro
Abstract We describe a chemo-enzymatic synthesis of modified nucleosides through lipase-catalyzed hydrolysis of their peracetylated precursors. It was found from screening of a large number of substrates that these enzymes' regioselectivities were affected by the sugar and the nucleobase structures. By selecting the best enzyme for each substrate in terms of activity and regioselectivity, we prepared a small library of differently monodeprotected purine and pyrimidine nucleosides useful as intermediates for the synthesis of high-value nucleosides and mononucleotides. By this approach, the chemo-enzymatic preparation of doxifluridine (14) anduridine 5,-monophosphate (5,-UMP, 15) from peracetylated uridine 1 was carried out. Elimination of many of the processing stages associated with existing methods was achieved, and higher yields and products of increased purity were generated. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

A new chemical method of synthesis of modified nucleoside [32P]phosphates

Unambiguous structural elucidation of base-modified purine nucleosides using NMR

MAGNETIC RESONANCE IN CHEMISTRY, Issue 1 2008
Raman Narukulla
Abstract A general and unambiguous approach has been developed for structural elucidation of modified purine nucleosides using NMR spectroscopy. Systematic assignment of proton and carbon signals of modified nucleosides was firmly established by COSY and the anomerism of the glycosidic linkage of synthetic nucleosides clearly elucidated by NOESY experiments. Characteristic properties of 15N-isotopic labelling at specific positions of nucleosides were also employed for structural studies. The reported approach is applicable to other modified nucleosides and nucleotides, as well as nucleobases. Copyright © 2007 John Wiley & Sons, Ltd. [source]