5975-18-8

Usage

Uses

Used in Pharmaceutical Industry:
Tributylammonium pyrophosphate is used as a reactant for the enzymic synthesis of 3′-deoxy-apio-nucleic acid duplexes, which are essential in the development of novel drugs and therapies targeting various diseases.
Used in Chemical Synthesis:
In the field of chemical synthesis, tributylammonium pyrophosphate is used as a reactant for the synthesis of deoxynucleoside S-methylphosphonic acids. These compounds have potential applications in the development of new pharmaceuticals and chemical agents.
Used in Biochemistry Research:
Tributylammonium pyrophosphate is used in the preparation of fluorescent non-nucleotide ATP analog N-methylanthraniloylamideethyl triphosphate. This analog is valuable for research purposes, particularly in the study of enzyme mechanisms and cellular processes.
Used in Nucleotide Synthesis:
Due to its low water content and high solubility in organic solvents, tributylammonium pyrophosphate is useful in the synthesis of triphosphates, which are crucial for various biological processes and applications in the fields of molecular biology and genetics.
Used in Structural Biology:
Tributylammonium pyrophosphate has been employed in the preparation of structurally complex dinucleotide-5'-triphosphates, which are important for understanding the structure and function of nucleic acids and their interactions with proteins and other molecules.

Preparation

A solution of tetrasodium pyrophosphate (3.5 g, 7.5 mmol) in water (50 mL) was eluted through a cation exchange resin (BIO-RAD AG 50 W-X8 Resin, 50–100 mesh, hydrogen form) at 4 °C. The eluent with pH of less than 3 (pH paper) was collected directly into a vigorously stirred flask containing tributylamine (2 mL, 8 mmol, 4 °C). The obtained tributylammonium pyrophosphate was dried through repeated rotary evaporation with dry MeOH and then dissolved in dry DMF (10 mL).

References

Santner et al (2012). The synthesis of 2′-methylseleno adenosine and guanosine 5′-triphosphates. Bioorganic and Medicinal Chemistry 20:2416.Hollenstein (2012). Nucleoside Triphosphates — Building Blocks for the Modification of Nucleic Acids. Molecules 17:13569-13591.bramova et al (2007). A facile and effective synthesis of dinucleotide 5′-triphosphates. Bioorganic and Medicinal Chemistry 15:6549-6555.

Upstream product

• 102-82-9 tributyl-amine 
• 86119-84-8 phosphoric acid 

Downstream Products

• 90015-82-0 5-[3-aminoallyl]-2'-deoxy-uridine 5'-triphosphate 
• 79551-89-6 L(-)FMAUTP 
• 35542-01-9 5-methoxycarbonylmethyl-2'-O-methyl-uridine 
• 138284-89-6 (1R,4S)-2-Amino-1,9-dihydro-9-<4-(hydroxymethyl)cyclopent-2-enyl>purin-6-one Triphosphate 

Relevant academic research and scientific papers

Synthesis of 8-oxo-dGTP and its β,γ-CH2-, β,γ-CHF-, and β,γ-CF2- analogues

Three novel bisphosphonate analogues of 8-oxo-dGTP 3 in which the bridging β,γ-oxygen is replaced by a methylene, fluoromethylene or difluoromethylene group (4–6, respectively) have been synthesized from 8-oxo-dGMP 2 by reaction of its morpholine 5′-phosphoramidate 14 or preferably, its N-methylimidazole 5′-phosphoramidate 15 with tri-n-butylammonium salts of the appropriate bisphosphonic acids, 11–13. The latter method also provides a convenient new route to 3. Analogues 4–6 may be useful as mechanistic probes for the role of 3 in abnormal DNA replication and repair.

Aptamer-based proximity labeling guides covalent RNA modification

We describe the development of a proximity-induced bio-orthogonal inverse electron demand Diels-Alder reaction that exploits the high-affinity interaction between a dienophile-modified RhoBAST aptamer and its tetramethyl rhodamine methyltetrazine substrate. We applied this concept for covalent RNA labeling in proof-of-principle experiments.

Preparation method of P,P-di(uridine 5'-)tetraphosphate

The invention relates to a preparation method of P,P-di(uridine 5'-)tetraphosphate. The method comprises the following steps: under the action of a metal salt catalyst, imidazole triethylamine pyrophosphate shown in formula I and uridine monophosphate triethylamine salt shown in formula II react in N,N-dimethylformamide, and P,P-di(uridine 5'-)tetraphosphate shown in formula III is obtained.

Debranchase-resistant labeling of RNA using the 10DM24 deoxyribozyme and fluorescent modified nucleotides

The 10DM24 deoxyribozyme can site-specifically label RNAs with fluorophore-GTP conjugates; however, the 2′,5′-branched RNA linkage is readily cleaved by debranchase. To prevent loss of labels upon cleavage, we synthesized phosphorothioate-modified, fluore

Method of preparing phosphate

The invention provides a method of preparing a phosphate. The method comprises the following step: enabling a pyrophosphate active compound expressed by formula II to react with uridine monophosphate expressed by a formula III or a salt thereof in a hydrophilic solvent under the action of a bimetallic ion composite catalyst to obtain P1,P4-bis (5'-uridine group) tetraphosphate expressed by formula I. In the formula II, X is imidazolyl, N-methyl imidazolyl, or 1, 2, 4-triazolyl; and the bimetallic ions in the bimetallic ion composite catalyst are a combination of any two of Zn2+, Mn2+, Mg2+, Fe2+, Fe3+ and Al3+. The method of preparing a phosphate employs a bimetallic catalytic system and can achieve high-efficiency and easy separation preparation of diquafosol.

Solid-phase synthesis of oligonucleotide 5a?2-(?±-P-Thio)triphosphates and 5a?2-(?±-P-Thio)(?2,?3-methylene)triphosphates

A robust solid-phase synthesis was developed to obtain original oligonucleotides (ONs) functionalized at their 5a?2 end with modified triphosphate (TP) moieties, in which a nonbridging oxygen atom of the ?± phosphorus atom was replaced by a sulfur atom and the labile P-O-P linkage was changed into a methylene bridge between the ?2 and ?3 phosphorus atoms. The efficient method is based on solid-supported ON assembly followed by 5a?2-H-phosphonylation, oxidation to the thiophosphate subsequently activated as a phosphoanhydride with diphenyl phosphoryl chloride, then nucleophilic substitution with the alkylammonium salt of pyrophosphate or its ?2,?3-methylene analogue. After deprotection and release from the solid support under basic conditions, 5a?2-(?±-P-thio)-TP and 5a?2-(?±-P-thio)(?2,?3-methylene)TP oligonucleotides were obtained in satisfactory yields, and they were isolated with high purity. These hydrolysis-resistant 5a?2-TP ONs will be useful in biological research to elucidate the mechanism of enzymes involved in mRNA processing and maturation.

Synthesis and anti-HIV activity of a series of 6-modified 2′,3′-dideoxyguanosine and 2′,3′-didehydro-2′, 3′-dideoxyguanosine analogs

In search of potential 2′,3′-dideoxyguanosine (ddG) and 2′,3′-didehydro-2′,3′-dideoxyguanosine (D4G) prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cytotoxities in cell-based assays. All analogs showed low cytotoxicities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile one-pot method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase (RT) incorporated in DNA/RNA strands were investigated by a non-radioactivity method and K m were determined. A series of 6-modified 2′,3′- dideoxyguanosine and 2′,3′-didehydro-2′,3′- dideoxyguanosine analogs were synthesized. Anti-HIV activity was investigated in cell-based assay. ddGTP was synthesized as well as D4TTP by a novel one-pot method, and the incorporation efficiencies recognized by DNA polymerase and HIV reverse transcriptase (HIV RT) were evaluated. Copyright

4-Alkyloxyimino-cytosine nucleotides: Tethering approaches to molecular probes for the P2Y6 receptor

4-Alkyloxyimino derivatives of pyrimidine nucleotides display high potency as agonists of certain G protein-coupled P2Y receptors (P2YRs). In an effort to functionalize a P2Y6R agonist for fluorescent labeling, we probed two positions (N4 and γ-phosphate of cytidine derivatives) with various functional groups, including alkynes for click chemistry. Functionalization of extended imino substituents at the 4 position of the pyrimidine nucleobase of CDP preserved P2Y6R potency generally better than γ-phosphoester formation in CTP derivatives. Fluorescent Alexa Fluor 488 conjugate 16 activated the human P2Y6R expressed in 1321N1 human astrocytoma cells with an EC50 of 9 nM, and exhibited high selectivity for this receptor over other uridine nucleotide-activated P2Y receptors. Flow cytometry detected specific labeling with 16 to P2Y 6R-expressing but not to wild-type 1321N1 cells. Additionally, confocal microscopy indicated both internalized 16 (t1/2 of 18 min) and surface-bound fluorescence. Known P2Y6R ligands inhibited labeling. Theoretical docking of 16 to a homology model of the P2Y6R predicted electrostatic interactions between the fluorophore and extracellular portion of TM3. Thus, we have identified the N4-benzyloxy group as a structurally permissive site for synthesis of functionalized congeners leading to high affinity molecular probes for studying the P2Y6R.

Adenosine Analogs and Their Use

The invention provides adenosine analog compounds that act at P2Y receptors, e.g., the P2Y2 receptor, including pharmaceutical compositions; and uses thereof to treat or prevent diseases associated with that receptor, e.g., disorders relating t

Frontal affinity chromatography-mass spectrometry useful for characterization of new ligands for GPR17 receptor

The application of frontal affinity chromatography-mass spectrometry (FAC-MS), along with molecular modeling studies, to the screening of potential drug candidates toward the recently deorphanized G-protein-coupled receptor (GPCR) GPR17 is shown. GPR17 is dually activated by uracil nucleotides and cysteinyl-leukotrienes, and is expressed in organs typically undergoing ischemic damage (i.e., braheart and kidney), thus representing a new pharmacological target for acute and chronic neurodegeneration. GPR17 was entrapped on an immobilized artificial membrane (IAM), and this stationary phase was used to screen a library of nucleotide derivatives by FAC-MS to select high affinity ligands. The chromatographic results have been validated with a reference functional assay ([35S]GTPγS binding assay). The receptor nucleotide-binding site was studied by setting up a column where a mutated GPR17 receptor (Arg255Ile) has been immobilized. The chromatographic behavior of the tested nucleotide derivatives together with in silico studies have been used to gain insights into the structure requirement of GPR17 ligands.