 | This articleneeds additional citations forverification. Please helpimprove this article byadding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Nucleoside analogue" – news ·newspapers ·books ·scholar ·JSTOR(December 2009) (Learn how and when to remove this message) |
 | You can helpexpand this article with text translated fromthe corresponding article in German. (December 2020)Click [show] for important translation instructions.
|
Nucleoside analogues arestructural analogues of anucleoside, which normally contain anucleobase and a sugar.Nucleotide analogues are analogues of anucleotide, which normally has one to threephosphates linked to a nucleoside. Both types of compounds can deviate from what they mimick in a number of ways, as changes can be made to any of the constituent parts (nucleobase, sugar, phosphate).[1] They are related tonucleic acid analogues.
Nucleoside and nucleotide analogues can be used in therapeutic drugs, including a range of antiviral products used to preventviral replication in infected cells. The most commonly used isacyclovir.
Nucleotide and nucleoside analogues can also be found naturally. Examples include ddhCTP (3ʹ-deoxy-3′,4ʹdidehydro-CTP) produced by the human antiviral proteinviperin[2] andsinefungin (aS-Adenosyl methionine analogue) produced by someStreptomyces.[3]
These agents can be used againsthepatitis B virus,hepatitis C virus,herpes simplex, andHIV. Once they arephosphorylated, they work asantimetabolites by being similar enough tonucleotides to be incorporated into growingDNA strands; but they act aschain terminators and stop viralDNA polymerase. They are not specific to viral DNA and also affectmitochondrial DNA. Because of this they have side effects such as bone marrow suppression.
There is a large family ofnucleoside analogue reverse transcriptase inhibitors, because DNA production byreverse transcriptase is very different from normal humanDNA replication, so it is possible to design nucleoside analogues that are preferentially incorporated by the former. Some nucleoside analogues, however, can function both as NRTIs and polymerase inhibitors for other viruses (e.g., hepatitis B).
Less selective nucleoside analogues are used aschemotherapy agents to treatcancer, e.g.gemcitabine. They are also used asantiplatelet drugs to prevent the formation of blood clots,ticagrelor andcangrelor.
Resistance can develop quickly with as little as one mutation.[4] Mutations occur in the enzymes that phosphorylate the drug and activate it: in the case ofherpes simplex, resistance toacyclovir[5] arises due to a mutation affecting the viral enzymethymidine kinase[6]. Since nucleoside analogues require two phosphorylations to be activated, one carried out by a viral enzyme and the other by enzymes in the host cell, mutations in viral thymidine kinase interfere with the first of these phosphorylations; in such cases the drug remains ineffective. There are, however, several different nucleoside analogue drugs and resistance to one of them is usually overcome by switching to another drug of the same kind (e.g.famciclovir,penciclovir,valaciclovir).
Nucleoside analogue drugs include:
Related drugs arenucleobase analogs, which don't include a sugar or sugar analog, andnucleotide analogues, which also include phosphate groups.