Nucleosides are glycosylamines that are similar to nucleotides but do not contain a phosphate group. A nucleoside is made up of just a nucleobase (also known as a nitrogenous base) and a five-carbon sugar (ribose or 2′-deoxyribose), whereas a nucleotide has a nucleobase, a five-carbon sugar, and one or more phosphate groups. The anomeric carbon of a nucleoside is linked to the N9 of a purine or the N1 of a pyrimidine by a glycosidic bond. DNA and RNA are made up of nucleotides, which are the basic building blocks.
Use in medicine and technology
In medicine several nucleoside analogues are used as antiviral or anticancer agents.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.
Prebiotic synthesis of ribonucleosides
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. 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.
Nucleoside analogues are nucleosides which contain a nucleic acid analogue and a sugar. Nucleotide analogs are nucleotides which contain a nucleic acid analogue, a sugar, and a phosphate groups with one to three phosphates.
Nucleoside and nucleotide analogues can be used in therapeutic drugs, include a range of antiviral products used to prevent viral replication in infected cells. The most commonly used is acyclovir, although its inclusion in this category is uncertain, because it acts as a nucleoside but contains no actual sugar, as the sugar ring is replaced by an open-chain structure.
Nucleodide and nucleoside analogues can also be found naturally. Examples include ddhCTP (3ʹ-deoxy-3′,4ʹdidehydro-CTP) produced by the human antiviral protein viperin and sinefungin (a S-Adenosyl methionine analogue) procduced by some Streptomyces.
These agents can be used against hepatitis B virus, hepatitis C virus, herpes simplex, and HIV. Once they are phosphorylated, they work as antimetabolites by being similar enough to nucleotides to be incorporated into growing DNA strands; but they act as chain terminators and stop viral DNA polymerase. They are not specific to viral DNA and also affect mitochondrial DNA. Because of this they have side effects such as bone marrow suppression.