13957-31-8

Usage

Uses

Used in Bacterial Cell Growth:
4-Thiouridine is used as a nucleotide analog for cell growth in certain bacterial species, such as Escherichia coli. It can act as a built-in antiphotomutagenic agent that protects these cells against mutagenesis.
Used in RNA Analysis:
4-Thiouridine is used as a photoreactive (crosslinking) uridine analogue that, upon phosphorylation to 4-thioUTP, may be incorporated into RNA structures. It is used to study the specificity and kinetics of uridine-cytidine kinases and is widely used for RNA analysis, including RNA-RNA cross coupling and RNA labeling.
Used in RNA-Protein Structural Studies:
4-Thiouridine is used to modify oligos slated for RNA or RNA-protein structural studies. A 4-thio-rU modified RNA pentamer was used to study the effect of this modification on codon-anticodon interaction when it is in the wobble position of tRNA.
Used in Chelation of Metal Ions:
4-Thiouridine is also able to chelate with certain metal ions, making it useful in various applications where metal ion binding is required.

Biochem/physiol Actions

4-Thiouridine plays a role in assessing nascent RNA synthesis. It also enhances site-specific crosslinking. 4-Thiouridine also acts as a photoaffinity probe due to its stability even while lacking specific photoactivation. It can also be incorporated into RNAs.

InChI:InChI=1/C9H12N2O5S/c12-3-4-6(13)7(14)8(16-4)11-2-1-5(17)10-9(11)15/h1-2,4,6-8,12-14H,3H2,(H,10,15,17)

Upstream product

• 15049-50-0 1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)-4-thiouracil 
• 53337-88-5 2-methoxy-1-β-D-ribofuranosyl-pyrimidine-4-one 
• 136055-18-0 S-(2-cyanoethyl)-4-thiouridine 
• 59495-20-4 4-ethoxy-1-(β-D-ribofuranosyl)-2(1H)-pyrimidinone 
• 55003-25-3 4-thio-1-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-(3H)-pyrimidine-2,4-dione 
• 109389-25-5 1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methyl-4-(1H-1,2,4-triazol-1-yl)pyrimidin-2(1H)-one 
• 50-89-5 thymidine 
• 10457-18-8 3',5'-bis-O-(trimethylsilyl)-thymidine 
• 82913-19-7 [(2R,3R,4R)-3,4-diacetoxy-5-[2-oxo-4-(1,2,4-triazol-1-yl)pyrimidin-1-yl]tetrahydrofuran-2-yl]methyl acetate 
• 4105-38-8 Tri-O-acetyluridine 
• 136055-17-9 3-[1-((2R,3R,4R,5R)-3,4-Bis-trimethylsilanyloxy-5-trimethylsilanyloxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-4-ylsulfanyl]-propionitrile 
• 136055-16-8 2,4,6-Triisopropyl-benzenesulfonic acid 1-((2R,3R,4R,5R)-3,4-bis-trimethylsilanyloxy-5-trimethylsilanyloxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-4-yl ester 
• 58-96-8 uridine 
• 10457-16-6 2',3',5,-tris-O-(trimethylsilyl)uridine 

Downstream Products

• 144303-79-7 1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-4-methyldisulfanyl-1H-pyrimidin-2-one 
• 74972-87-5 S-(N-(4-anilino-1-naphthyl)carbamylmethyl)-4-thiouridine 
• 73719-79-6 4-phenacylthiouridine 
• 58-96-8 uridine 
• 136671-59-5 5'-O-dimethoxytrityl-4-thiouridine 
• 73719-83-2 1-β-D-ribofuranosyl-4-phenacylidene-2-(3H)-pyrimidone 
• 18427-02-6 Di-(4-deoxy-4-uridinyl)-disulfid 
• 31556-28-2 4-thiouridine 5'-triphosphate 
• 591-28-6 4-thiouracil 
• 4145-46-4 4-Thiouridin-5'-phosphat 
• 219709-47-4 4-S-pivaloyloxymethyl-5'-O-dimethoxytrityl-3'-O-tert-butyldimethylsilyl-4-thiouridine 
• 219709-48-5 4-S-pivaloyloxymethyl-2'-O-tert-butyldimethylsilyl-5'-O-dimethoxytrityl-4-thiouridine 
• 3258-02-4 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4-(hydroxylamino)pyrimidin-2(1H)-one 

Relevant academic research and scientific papers

Chemical Conversion of Uridine into 4-Thiouridine via the 4-(1,2,4-Triazol-1-yl)pyrimidin-2(1H)-one Intermediate

In an aqueous solution of sodium hydrosulphide at room temperature, 4-(1,2,4-triazol-1-yl)-1-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)pyrimidin-2(1H)-one, prepared from uridine, is converted into the 4-thiopyrimidin-2(1H)-one derivative which can be deacetylated to yield 4-thiouridine.

Synthesis and Metabolic Fate of 4-Methylthiouridine in Bacterial tRNA

Ribonucleic acid (RNA) is central to many life processes and, to fulfill its function, it has a substantial chemical variety in its building blocks. Enzymatic thiolation of uridine introduces 4-thiouridine (s4U) into many bacterial transfer RNAs (tRNAs), which is used as a sensor for UV radiation. A similar modified nucleoside, 2-thiocytidine, was recently found to be sulfur-methylated especially in bacteria exposed to antibiotics and simple methylating reagents. Herein, we report the synthesis of 4-methylthiouridine (ms4U) and confirm its presence and additional formation under stress in Escherichia coli. We used the synthetic ms4U for isotope dilution mass spectrometry and compared its abundance to other reported tRNA damage products. In addition, we applied sophisticated stable-isotope pulse chase studies (NAIL-MS) and showed its AlkB-independent removal in vivo. Our findings reveal the complex nature of bacterial RNA damage repair.

Anti-hepatitis B virus compound as well as preparation method and application thereof

The invention provides an anti-hepatitis B virus compound and a preparation method and application thereof, the compound is 4-thiouridine isobutyrate, the molecular formula is C13H18N2O6S, and the structural formula is shown in the specification. The compound provided by the invention can effectively inhibit the activity of hepatitis B virus, can be used as a substitute drug for lamivudine and telbivudine, solves the problem of drug resistance of lamivudine and the like in the aspect of resisting hepatitis B virus, is high in drug effect, low in toxicity and low in price, and provides a direction for development of drugs for treating hepatitis B. In addition, the invention discloses a preparation method of the compound 4-thiouridine isobutyrate, and the preparation method is mild in condition, easy to synthesize and suitable for industrial production.

SYNTHESIS AND STRUCTURE OF HIGH POTENCY RNA THERAPEUTICS

This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5′ UTRs, where a 5′ UTR may be expressed by a gene of a plant. In some embodiments, a 5′ UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.

Systematic assignment of NMR spectra of 5-substituted-4-thiopyrimidine nucleosides

Unambiguous characterization of 5-substituted-4-thiopyrimidine nucleosides (ribonucleosides and 2'-deoxynucleosides) was performed using NMR spectroscopy. Assignments of all proton and carbon signals of 5-bromo-4-thiouridine and related nucleosides were systematically carried out and firmly established by COSY and HMQC techniques. The NMR data of various 4-thiopyrimidine nucleosides are compared, and the key contributing factors discussed. The approach presented here is applicable to other modified nucleosides and nucleotides, as well as nucleobases. Copyright

Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors

A large series of derivatives and analogues of the uracil nucleotides UMP, UDP, and UTP with modifications in various positions of the uracil moiety and/or the phosphate groups were synthesized and evaluated at human P2Y2, P2Y4, and P2Y6 receptors. 2-(Ar)alkylthio substitution of UMP and UDP was best tolerated by the P2Y2 receptor. 2-Phenethylthio-UMP (13e) showed an EC50 value of 1.3 μM at P2Y2 and >70-fold selectivity versus P2Y4 and P2Y 6 receptors. Substitution of the 2-keto group in UMP by NH (13g, iso-CMP) resulted in the first potent and selective P2Y4 agonist (EC50 4.98 μM, >20-fold selective vs P2Y2 and P2Y6). In contrast, replacement of the 2-keto function in UDP by NH yielded a potent P2Y2 agonist (12g, iso-CDP, EC50 = 0.604 μM, >100-fold selective). In an attempt to obtain metabolically stable UTP analogues, β,γ-dichloro- and β,γ-difluoro-methylene-UTP derivatives were synthesized. The triphosphate modifications were much better tolerated by P2Y2, and in some cases also by P2Y6, than by P2Y4 receptors. 4-Thio-β,γ-difluoromethylene-UTP (14g) was a potent P2Y2 agonist with an EC50 value of 0.134 μM and >50-fold selectivity. N3-Phenacyl-β,γ-dichloromethylene- UTP (14b) proved to be a potent P2Y6 receptor agonist (EC 50 0.142 μM) with high selectivity versus P2Y4 (50-fold) and moderate selectivity versus P2Y2 receptors (6-fold).

Anti-HCV nucleoside derivatives

The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

4-Substituted uridine 5′-triphosphates as agonists of the P2y2 purinergic receptor

Undine 5′-O-triphosphate (UTP) is a potent agonist of the purinergic receptor designated P2Y2. UTP is rapidly metabolized in human tissue. To find a compound with similar activity that may be more slowly metabolized, a series of 4-substituted uridine 5′-triphosphates were prepared and evaluated in a P2Y2 receptor second messenger assay. Copyright

Convenient intermediates for the preparation of C-4 modified derivatives of pyrimidine nucleosides

4-(4-Nitrophenoxy)-1-(β-D-ribofuranosyl)pyrimidin-2(1H)-one 15, 5- methyl-4-(1,2,4-triazol-1-yl)-1-(β-D-2-deoxyribofuranosyl)pyrimidin-2(1H)- one 7a and 4-(4-nitrophenoxy)-1-(βD-2-deoxyribofuranosyl)pyrimidin-2(1H)- one 17a, respectively, have been prepared and are recommended as reactive intermediates for the preparation of derivatives of uridine, thymidine and 2'-deoxyuridine which are modified at C-4.

Synthesis and stability of S-cyanoethyl-protected 4-thiouridine and 2'-deoxy-4-thiouridine

A convenient preparation of S-(2-cyanoethyl) protected 2'-deoxy-4-thiouridine (5a) and 4-thiouridine (5b) is presented. The S-cyanoethyl protecting group is stable to reagents commonly encountered during the phosphoramidite method of solid-phase oligonucleotide synthesis, and is readily deprotected using concentrated NH4OH at 25°C.