[Modified nucleosides and nucleotides inhibiting HIV replication: analysis of the situation and potential prospects].
The results of an eight year search of blockaders of human immunodeficiency virus (HIV) among groups of modified nucleosides and nucleotides are reviewed. The molecular mechanism of action of these compounds is based on the inhibition of DNA polymerases activity. Attempts of systematic analysis of structure--anti-HIV activity relationship for modified substrates of DNA biosynthesis are made. In this analysis attention is focused on the evaluation of general properties of enzymes of the phosphorylation cascade and DNA polymerases. Such properties are analyzed on the basis of empiric rules which summarize electronic, steric and conformational properties of substrate analogs. The ability of phosphorylating nucleosides to block HIV reproduction are analyzed. The interdependence of structure of several most known inhibitors with their action on nucleic acids components metabolism as well as the structure--therapeutic properties relationship are discussed.
Kraevskiĭ
A A
AA
D006678:HIV / Q000502:physiology*; D009705:Nucleosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D009705:Nucleosides; D009711:Nucleotides
Modifitsirovannye nukleozidy i nukleotidy, podavliaiushchie reproduktsiiu VICh: analiz situatsii i veroiatnaia perspektiva.