Nucleoside

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deoxyadenosine
deoxyadenosine
adenosine
adenosine
Two corresponding nucleosides, the deoxyribonucleoside, deoxyadenosine, and the ribonucleoside, adenosine. Both are in line-angle representation, where the presence of carbon atoms are inferred at each angle, as are the hydrogen atoms attached to the carbon, to fill its valency (to having four bonds).

Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups. In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or the N1 of a pyrimidine. Examples of nucleosides include cytidine, uridine, adenosine, guanosine, thymidine and inosine.[1]

While a nucleoside is a nucleobase linked to a sugar, a nucleotide is composed of a nucleoside and one or more phosphate groups. Thus, nucleosides can be phosphorylated by specific kinases in the cell on the sugar's primary alcohol group (-CH2-OH) to produce nucleotides. Nucleotides are the molecular building-blocks of DNA and RNA.

Source[edit]

Nucleosides can be produced from nucleotides de novo, particularly in the liver, but they are more abundantly supplied via ingestion and digestion of nucleic acids in the diet, whereby nucleotidases break down nucleotides (such as the thymidine monophosphate) into nucleosides (such as thymidine) and phosphate. The nucleosides, in turn, are subsequently broken down in the lumen of the digestive system by nucleosidases into nucleobases and ribose or deoxyribose. In addition, nucleotides can be broken down inside the cell into nitrogenous bases, and ribose-1-phosphate or deoxyribose-1-phosphate.

Use in medicine and technology[edit]

In medicine several nucleoside analogues are used as antiviral or anticancer agents.[2][3][4] The viral polymerase incorporates these compounds with non-canonical bases. These compounds are activated in the cells by being converted into nucleotides. They are administered as nucleosides since charged nucleotides cannot easily cross cell membranes.

In molecular biology, several analogues of the sugar backbone exist. Due to the low stability of RNA, which is prone to hydrolysis, several more stable alternative nucleoside/nucleotide analogues that correctly bind to RNA are used. This is achieved by using a different backbone sugar. These analogues include locked nucleic acids (LNA), morpholinos and peptide nucleic acids (PNA).

In sequencing, dideoxynucleotides are used. These nucleotides possess the non-canonical sugar dideoxyribose, which lacks 3' hydroxyl group (which accepts the phosphate). It therefore cannot bond with the next base and terminates the chain, as DNA polymerases cannot distinguish between it and a regular deoxyribonucleotide.

Nitrogenous base Ribonucleoside Deoxyribonucleoside
Chemical structure of adenine
Adenine

A

Chemical structure of adenosine
Adenosine
Chemical structure of deoxyadenosine
Deoxyadenosine
dA
Chemical structure of guanine
Guanine

G

Chemical structure of guanosine
Guanosine
Chemical structure of deoxyguanosine
Deoxyguanosine
dG
Chemical structure of thymine
Thymine
T
Chemical structure of 5-methyluridine
5-Methyluridine
m5U
Chemical structure of thymidine
Thymidine
dT
Chemical structure of uracil
Uracil
U
Chemical structure of uridine
Uridine
Chemical structure of deoxyuridine
Deoxyuridine
dU
Chemical structure of cytosine
Cytosine
C
Chemical structure of cytidine
Cytidine
Chemical structure of deoxycytidine
Deoxycytidine
dC

Prebiotic synthesis of ribonucleosides[edit]

In order to understand how life arose, knowledge is required of the chemical pathways that permit formation of the key building blocks of life under plausible prebiotic conditions. According to the RNA world hypothesis free-floating ribonucleosides and ribonucleotides were present in the primitive soup. Molecules as complex as RNA must have arisen from small molecules whose reactivity was governed by physico-chemical processes. RNA is composed of purine and pyrimidine nucleotides, both of which are necessary for reliable information transfer, and thus Darwinian natural selection and evolution. Nam et al.[5] demonstrated the direct condensation of nucleobases with ribose to give ribonucleosides in aqueous microdroplets, a key step leading to RNA formation. Also, a plausible prebiotic process for synthesizing pyrimidine and purine ribonucleosides and ribonucleotides using wet-dry cycles was presented by Becker et al. [6]

See also[edit]

References[edit]

  1. ^ Nelson, David L.; Cox, Michael M. (2005). Principles of Biochemistry (4th ed.). New York: W. H. Freeman. ISBN 0-7167-4339-6.
  2. ^ Galmarini, Carlos M.; MacKey, John R.; Dumontet, Charles (2002). "Nucleoside analogues and nucleobases in cancer treatment". The Lancet Oncology. 3 (7): 415–424. doi:10.1016/S1470-2045(02)00788-X. PMID 12142171.
  3. ^ Jordheim, Lars Petter; Durantel, David; Zoulim, Fabien; Dumontet, Charles (2013). "Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases". Nature Reviews Drug Discovery. 12 (6): 447–464. doi:10.1038/nrd4010. PMID 23722347. S2CID 39842610.
  4. ^ Ramesh, Deepthi; Vijayakumar, Balaji Gowrivel; Kannan, Tharanikkarasu (12 February 2021). "Advances in Nucleoside and Nucleotide Analogues in Tackling Human Immunodeficiency Virus and Hepatitis Virus Infections". ChemMedChem. doi:10.1002/cmdc.202000849. Retrieved 13 March 2021.
  5. ^ Nam I, Nam HG, Zare RN. Abiotic synthesis of purine and pyrimidine ribonucleosides in aqueous microdroplets. Proc Natl Acad Sci U S A. 2018 Jan 2;115(1):36-40. doi: 10.1073/pnas.1718559115. Epub 2017 Dec 18. PMID: 29255025; PMCID: PMC5776833
  6. ^ Becker S, Feldmann J, Wiedemann S, Okamura H, Schneider C, Iwan K, Crisp A, Rossa M, Amatov T, Carell T. Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides. Science. 2019 Oct 4;366(6461):76-82. doi: 10.1126/science.aax2747. PMID: 31604305.

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