Nucleoside

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]

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).

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.

SourceEdit

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 technologyEdit

In medicine several nucleoside analogues are used as antiviral or anticancer agents.[2][3] 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 LNA, morpholino, 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
 
Adenine
 
Adenosine
A
 
Deoxyadenosine
dA
 
Guanine
 
Guanosine
G
 
Deoxyguanosine
dG
 
Thymine
 
5-Methyluridine
m5U
 
Thymidine
dT
 
Uracil
 
Uridine
U
 
Deoxyuridine
dU
 
Cytosine
 
Cytidine
C
 
Deoxycytidine
dC

See alsoEdit

ReferencesEdit

  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.