Lnucleoside

L-nucleoside refers to a nucleoside whose pentose sugar is in the left-handed configuration, the mirror image of the natural D-ribose nucleosides found in DNA and RNA. As a result, their three-dimensional shape differs from their natural counterparts, which can influence interactions with cellular enzymes and viral polymerases. L-nucleosides are relatively rare in nature but can be prepared by asymmetric synthesis or chiral resolution. Their biological activity is often governed by stereochemistry, with many L-nucleosides being poor substrates for human kinases and polymerases, while some viral enzymes can accommodate them, yielding potent antiviral effects.

In clinical chemistry, several L-nucleoside antivirals are well known. Lamivudine (3TC) and emtricitabine (FTC) are cytidine analogs that adopt the L-configuration; telbivudine is a thymidine analog also used against hepatitis B. These agents are phosphorylated intracellularly to active triphosphates, which act as chain terminators upon incorporation by viral reverse transcriptases or polymerases. The L-configuration can contribute to selectivity and reduced toxicity, though it often results in different pharmacokinetics and resistance profiles compared with D-nucleoside analogs.

Research on L-nucleosides continues to explore their potential advantages in antiviral therapy and as tools for studying enzyme specificity. Synthesis, chiral separation, and evaluation of kinase efficiency remain key areas of development.