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In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecular precursor of nucleic acids. Nucleotides are the basic building blocks of DNA and RNA. Ribonucleotides themselves are basic monomeric building blocks for RNA. Deoxyribonucleotides, formed by reducing ribonucleotides with the enzyme ribonucleotide reductase (RNR), are essential building blocks for DNA. There are several differences between DNA deoxyribonucleotides and RNA ribonucleotides. Successive nucleotides are linked together via phosphodiester bonds.
Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and cervical cancer. In sickle-cell disease it increases fetal hemoglobin and decreases the number of attacks. It is taken by mouth.
A nucleoside triphosphate is a nucleoside containing a nitrogenous base bound to a 5-carbon sugar, with three phosphate groups bound to the sugar. They are the molecular precursors of both DNA and RNA, which are chains of nucleotides made through the processes of DNA replication and transcription. Nucleoside triphosphates also serve as a source of energy for cellular reactions and are involved in signalling pathways.
Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase (rNDP), is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of the ribose ring of nucleoside diphosphates. This reduction produces deoxyribonucleotides. Deoxyribonucleotides in turn are used in the synthesis of DNA. The reaction catalyzed by RNR is strictly conserved in all living organisms. Furthermore, RNR plays a critical role in regulating the total rate of DNA synthesis so that DNA to cell mass is maintained at a constant ratio during cell division and DNA repair. A somewhat unusual feature of the RNR enzyme is that it catalyzes a reaction that proceeds via a free radical mechanism of action. The substrates for RNR are ADP, GDP, CDP and UDP. dTDP is synthesized by another enzyme from dTMP.
Thioredoxin reductases are enzymes that reduce thioredoxin (Trx). Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. In bacteria TrxR also catalyzes the reduction of glutaredoxin like proteins known as NrdH. Both classes are flavoproteins which function as homodimers. Each monomer contains a FAD prosthetic group, a NADPH binding domain, and an active site containing a redox-active disulfide bond.
3-Aminopyridine-2-carboxaldehyde thiosemicarbazone is a substance that is being studied in the treatment of cancer.
Clofarabine is a purine nucleoside antimetabolite marketed in the United States and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. It is FDA-approved for treating relapsed or refractory acute lymphoblastic leukaemia (ALL) in children after at least two other types of treatment have failed. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out. Ongoing trials are assessing its efficacy for managing other cancers.
Endostatin is a naturally occurring, 20-kDa C-terminal fragment derived from type XVIII collagen. It is reported to serve as an anti-angiogenic agent, similar to angiostatin and thrombospondin.
Synergistic enhancers of antiretrovirals usually do not possess any antiretroviral properties alone, but when they are taken concurrently with antiretroviral drugs they enhance the effect of that drug.
Deoxyadenosine triphosphate (dATP) is a nucleotide used in cells for DNA synthesis, as a substrate of DNA polymerase. It is classified as a purine nucleoside triphosphate, with its chemical structure consisting of a deoxyribose sugar molecule bound to an adenine and to three phosphate groups. It differs from the energy-transferring molecule adenosine triphosphate (ATP) by a single hydroxyl group, resulting in a deoxyribose instead of a ribose. Two phosphate groups can be hydrolyzed to yield deoxyadenosine monophosphate, which can then be used to synthesize DNA.
Thymidylate synthase (TS) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUMP arise. Both cause DNA damage.
Motexafin gadolinium is an inhibitor of thioredoxin reductase and ribonucleotide reductase. It has been proposed as a possible chemotherapeutic agent in the treatment of brain metastases.
Cell synchronization is a process by which cells in a culture at different stages of the cell cycle are brought to the same phase. Cell synchrony is a vital process in the study of cells progressing through the cell cycle as it allows population-wide data to be collected rather than relying solely on single-cell experiments. The types of synchronization are broadly categorized into two groups; physical fractionization and chemical blockade.
Gallium maltolate is a coordination complex consisting of a trivalent gallium cation coordinated to three maltolate ligands. The compound is a potential therapeutic agent for cancer, infectious disease, and inflammatory disease. A cosmetic skin cream containing gallium maltolate is marketed under the name Gallixa. It is a colorless solid with significant solubility in both water and lipids.
Ribonucleoside-diphosphate reductase large subunit is an enzyme that in humans is encoded by the RRM1 gene.
Gallium nitrate (brand name Ganite) is the gallium salt of nitric acid with the chemical formula Ga(NO3)3. It is a drug used to treat symptomatic hypercalcemia secondary to cancer. It works by preventing the breakdown of bone through the inhibition of osteoclast activity, thus lowering the amount of free calcium in the blood. Gallium nitrate is also used to synthesize other gallium compounds.
Tezacitabine is a ribonucleotide reductase inhibitor. It is a synthetic purine nucleoside analogue with potential antineoplastic activity. It is used in synthetic DNA.
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit. TKIs are typically used as anticancer drugs. For example, they have substantially improved outcomes in chronic myelogenous leukemia. They have also been used to treat other diseases, such as idiopathic pulmonary fibrosis.
Ribonucleoside-diphosphate reductase subunit M2, also known as ribonucleotide reductase small subunit, is an enzyme that in humans is encoded by the RRM2 gene.
Induced cell cycle arrest is the use of a chemical or genetic manipulation to artificially halt progression through the cell cycle. Cellular processes like genome duplication and cell division stop. It can be temporary or permanent. It is an artificial activation of naturally occurring cell cycle checkpoints, induced by exogenous stimuli controlled by an experimenter.
References
- ↑ Zahedi Avval F, Berndt C, Pramanik A, Holmgren A (January 2009). "Mechanism of inhibition of ribonucleotide reductase with motexafin gadolinium (MGd)". Biochem. Biophys. Res. Commun. 379 (3): 775–9. doi:10.1016/j.bbrc.2008.12.128. PMID 19121624.
- ↑ Mayhew CN, Phillips JD, Cibull ML, Elford HL, Gallicchio VS (September 2002). "Short-term treatment with novel ribonucleotide reductase inhibitors Trimidox and Didox reverses late-stage murine retrovirus-induced lymphoproliferative disease with less bone marrow toxicity than hydroxyurea". Antivir. Chem. Chemother. 13 (5): 305–14. doi: 10.1177/095632020201300506 . PMID 12630679.
- ↑ Tsimberidou AM, Alvarado Y, Giles FJ (August 2002). "Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies". Expert Rev Anticancer Ther. 2 (4): 437–48. doi:10.1586/14737140.2.4.437. PMID 12647987. S2CID 30047759.
- ↑ Bernstein LR (1998). "Mechanisms of therapeutic activity for gallium" (PDF). Pharmacol. Rev. 50 (4): 665–682. PMID 9860806.
- ↑ Bitonti, A. J.; Dumont, J. A.; Bush, T. L.; Cashman, E. A.; Cross-Doersen, D. E.; Wright, P. S.; Matthews, D. P.; McCarthy, J. R.; Kaplan, D. A. (15 March 1994). "Regression of human breast tumor xenografts in response to (E)-2'-deoxy-2'-(fluoromethylene)cytidine, an inhibitor of ribonucleoside diphosphate reductase". Cancer Research. 54 (6): 1485–1490. PMID 8137252.
- ↑ "Tezacitabine monohydrate".
