63-38-7

Usage

Definition

ChEBI: A pyrimidine ribonucleoside 5'-diphosphate having cytosine as the nucleobase.

Upstream product

• 1623-07-0 monobenzylphosphate 
• 63-37-6 cytidine monophosphate 
• 69673-09-2 cytidine-5'-phosphoro-(2-aminoimidazole) 
• 85179-51-7 cytidine-5'-(2-methylimidazol-1-yl phosphate) 
• 76947-02-9 tris(tetra-n-butylammonium) hydrogen pyrophosphate 
• 50615-57-1 5'-O-tosylcytidine 
• 65-47-4 cytidine triphosphate 
• 107201-93-4 2',3'-O-(methoxymethylidene)-4-N-<(dimethylamino)methylene>cytidine 
• 107201-94-5 2',3'-O-(methoxymethylidene)-5'-O-tosyl-4-N-<(dimethylamino)methylene>cytidine 
• 6323-99-5 2-amino-4-phosphonobutyric acid 
• 65-46-3 CYTIDINE 
• 16628-82-3 2',3'-O-(methoxymethylidene)cytidine 

Downstream Products

• 65-47-4 cytidine triphosphate 
• 820-11-1 3-phosphoglyceric acid 
• 2906-23-2 CDP-glucose 
• 800-73-7 dCDP 

Relevant academic research and scientific papers

DUAL-ACTIVITY NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE INHIBITORS

The present disclosure describes NAMPT modulatory compounds, and methods of identifying NAMPT modulatory compounds. The present disclosure also describes methods of testing NAMPT modulatory compounds for NTPase activity, cell mobility modulatory activity, and cell metastasis modulatory activity.

Deciphering the Late Biosynthetic Steps of Antimalarial Compound FR-900098

FR-900098 is a potent chemotherapeutic agent for the treatment of malaria. Here we report the heterologous production of this compound in Escherichia coli by reconstructing the entire biosynthetic pathway using a three-plasmid system. Based on this system, whole-cell feeding assays in combination with in vitro enzymatic activity assays reveal an unusual functional role of nucleotide conjugation and lead to the complete elucidation of the previously unassigned late biosynthetic steps. These studies also suggest a biosynthetic route to a second phosphonate antibiotic, FR-33289. A thorough understanding of the FR-900098 biosynthetic pathway now opens possibilities for metabolic engineering in E. coli to increase production of the antimalarial antibiotic and combinatorial biosynthesis to generate novel derivatives of FR-900098.

Mechanism of activation of β-D-2′-Deoxy-2′-fluoro- 2′-C-methylcytidine and inhibition of hepatitis C virus NS5B RNA polymerase

β-D-2′-Deoxy-2′-fluoro-2′-C-methylcytidine (PSI-6130) is a potent specific inhibitor of hepatitis C virus (HCV) RNA synthesis in Huh-7 replicon cells. To inhibit the HCV NS5B RNA polymerase, PSI-6130 must be phosphorylated to the 5′-triphosphate form. The phosphorylation of PSI-6130 and inhibition of HCV NS5B were investigated. The phosphorylation of PSI-6130 by recombinant human 2′-deoxycytidine kinase (dCK) and uridine-cytidine kinase 1 (UCK-1) was measured by using a coupled spectrophotometric reaction. PSI-6130 was shown to be a substrate for purified dCK, with a Km of 81 μM and a kcat of 0.007 s -1, but was not a substrate for UCK-1. PSI-6130 monophosphate (PSI-6130-MP) was efficiently phosphorylated to the diphosphate and subsequently to the triphosphate by recombinant human UMP-CMP kinase and nucleoside diphosphate kinase, respectively. The inhibition of wild-type and mutated (S282T) HCV NS5B RNA polymerases was studied. The steady-state inhibition constant (Ki) for PSI-6130 triphosphate (PSI-6130-TP) with the wild-type enzyme was 4.3 μM. Similar results were obtained with 2′-C-methyladenosine triphosphate (Ki = 1.5 μM) and 2′-C-methylcytidine triphosphate (Ki = 1.6 μM). NS5B with the S282T mutation, which is known to confer resistance to 2′-C- methyladenosine, was inhibited by PSI-6130-TP as efficiently as the wild type. Incorporation of PSI-6130-MP into RNA catalyzed by purified NS5B RNA polymerase resulted in chain termination. Copyright

Convenient synthesis of nucleoside-5′-diphosphates from the corresponding ribonucleoside-5′-phosphoroimidazole

The reaction of ribonucleoside-5′-phosphoroimidazolide with a tributylammonium orthophosphate in anhydrous dimethylformamide at room temperature provides a general method for the synthesis of nucleoside-5′- diphosphate. The novelty of the approach is to use the triethylammonium salt of 5′-monophosphate nucleoside derivative prior to the imidazolate reaction with imidazole, triphenylphosphine, and 2,2′-dithiodipyridine. Deprotection, followed by displacement of the imidazole moiety using tributylammonium orthophosphate and a catalytic amount of zinc chloride in dimethylformamide gave the desired 5′-diphosphate products. The triethyl ammonium salt of 5′-diphosphate nucleosides was purified by flash chromatography using DEAE (diethylaminoethyl weak anion exchange resin) Sepharosa fast flow packed in an XK 50/60 column on an Akta FPLC (Fast Protein Liquid Chromatography). Synthesis procedures are reported for adenosine-5′-diphosphate, uridine-5′-diphosphate, cytidine-5′-diphosphate, and guanosine-5′-diphosphate. Yields for the displacement reactions ranged from 95 to 97%. Thus, this method offers the advantages of shorter reaction time, greater product yield, and a more cost-effective synthetic route. Copyright Taylor & Francis Group, LLC.

Borate-nucleotide complex formation depends on charge and phosphorylation state

Flow injection analysis with electrospray ionization mass spectrometry was used to investigate borate-nucleotide complex formation. Solutions containing 100 μM nucleotide and 500 μM boric acid in water-acetonitrile-triethylamine (50:50:0.2, v/v/v; pH 10.3

Structural analysis of the activation of ribavirin analogs by NDP kinase: Comparison with other ribavirin targets

Ribavirin used in therapies against hepatitis C virus (HCV) is potentially efficient against other viruses but presents a high cytotoxicity. Several ribavirin triphosphate analogs modified on the ribose moiety were synthesized and tested in vitro on the RNA polymerases of HCV, phage T7, and HIV-1 reverse transcriptase. Modified nucleotides with 2′-deoxy, 3′-deoxy, 2′,3′-dideoxy, 2′,3′-dideoxy-2′,3′-dehydro, and 2′,3′-epoxy-ribose inhibited the HCV enzyme but not the other two polymerases. They were also analyzed as substrates for nucleoside diphosphate (NDP) kinase, the enzyme responsible for the last step of the cellular activation of antiviral nucleoside analogs. An X-ray structure of NDP kinase complexed with ribavirin triphosphate was determined. It demonstrates that the analog binds as a normal substrate despite the modified base and confirms the crucial role of the 3′-hydroxyl group in the phosphorylation reaction. The 3′-hydroxyl is required for inhibition of the initiation step of RNA synthesis by HCV polymerase, and both sugar hydroxyls must be present to inhibit elongation. The 2′deoxyribavirin is the only derivative efficient in vitro against HCV polymerase and properly activated by NDP kinase.

Rapid photolytic release of cytidine 5′-diphosphate from a coumarin derivative: a new tool for the investigation of ribonucleotide reductases

In order to study the long-range radical transfer in the Escherichia coli ribonucleotide reductase (RNR), caged cytidine 5′-diphosphate (CDP) 1 was synthesized, which contains the photolabile (7-diethylaminocoumarin-4-Yl)methyl moiety. The cages CDP 1 triggers the release of CDP when irradiated at wavelengths between 365 and 436 nm. The rate constant of the formation of alcohol 2 and cytidine 5′-diphosphate 3 is 2×108 s- and the quantum efficiency for the disappearance of caged CDP 1 is 2.9%. Copyright

Identification of enzymes catalyzing two-step phosphorylation of cidofovir and the effect of cytomegalovirus infection on their activities in host cells

Cidofovir [CDV; (S)-1-(3-hydroxy-2-phosphonomethoxyethyl)-cytosine] is an acyclic nucleotide analog with potent and selective in vitro and in vivo activities against a broad spectrum of herpesviruses and other DNA viruses. We studied the mechanism of enzymatic synthesis of CDV diphosphate, the putative antiviral metabolite of CDV. The phosphorylation is two-step process catalyzed by several enzymes. An enzymatic activity phosphorylating CDV to its monophosphate derivative was purified from human liver and identified as pyrimidine nucleoside monophosphate kinase (EC 2.7.4.14.). CDV (K(m) = 2.10 ± 0.18 mM and V(max) = 1.10 ± 0.05 μmol/min/mg) was found to be a substantially weaker substrate for purified enzyme than CMP, UMP, or dCMP. Pyrimidine nucleoside monophosphate kinase was used for preparative enzymatic synthesis of CDV monophosphate. Pyruvate kinase (EC 2.7.1.40), creatine kinase (EC 2.7.3.2), and nucleoside diphosphate kinase (EC 2.7.4.6) were found to catalyze CDV diphosphate synthesis from CDV monophosphate, whereas phosphoglycerate kinase (EC 2.7.2.3) and succinyl-CoA synthetase (EC 6.2.1.4) did not. Based on V(max)/K(m) (phosphorylation efficiency) values determined with enzymes purified from human sources, the most efficient phosphorylation of CDV monophosphate is catalyzed by pyruvate kinase. After infection of human lung fibroblasts with cytomegalovirus, the intracellular activities of pyrimidine nucleoside monophosphate kinase, pyruvate kinase, creatine kinase, and nucleoside diphosphate kinase increased 2-, 1.3-, 3-, and 5-fold, respectively. The metabolism of [3H]CDV in mock- and cytomegalovirus-infected cells was examined. The intracellular levels of CDV monophosphate and CDV diphosphate increased ~20- and 8-fold, respectively, in cytomegalovirus-infected cells, presumably due to the stimulation of CDV uptake and higher activities of phosphorylating enzymes.

Nucleoside-Triphosphatase Activity of an ATP-Dependent Enzyme, N-Methylhydantoin Amidohydrolase

N-Methylhydantoin amidohydrolase, which catalyzes ATP-dependent hydrolysis of N-methylhydantoin to N-carbamoylsarcosine, was found to hydrolyze several nucleoside triphosphates to nucleoside diphosphates not only in the presence but also in the absence of amide substrates.Amide substrates, such as N-methylhydantoin and dihydrouracil, seem to be absolutely necessary for hydrolysis of ATP and dATP.However, N-methylhydantoin inhibited the hydrolysis of nucleoside triphosphates other than ATP and dATP.The kinetic data suggest that the presence of an amide substrate changes the affinity of the enzyme toward nucleoside triphosphates.

Mg(II) ION-MEDIATED CONVERSION OF MONO- AND OLIGONUCLEOTIDES TO 5'-POLYPHOSPHATES IN AQUEOUS SOLUTION

5'-Polyphosphates of mono- and oligonucleotides were prepared from the corresponding 5'-monophosphates with phosphorotriimidazolide or phosphorotribenzimidazolide mediated by Mg(II) or Mn(II) ion in aqueous solution.