Increased stability and antiviral activity of 2'-O-phosphoglyceryl derivatives of (2'-5')oligo(adenylate).
Metabolically stable analogues of (2'-5')oligo(adenylate), (2'-5')(A)n, might constitute a new class of antiviral agents as they mimic some of the effects of interferons. 2'-O-phosphoglyceryl derivatives of (2'-5')(A)n oligomers, (2'-5')(A)n-PGro have been synthesized by chemical modification of their terminal ribose residue. Such analogues are resistant to degradation by phosphodiesterases but remain sensitive to phosphatase activity, at least in cell-free extracts. In line with its increased stability, (2'-5')(A)n-PGro has a powerful antiviral activity against an RNA virus when microinjected with micropipettes into the cytoplasm of intact cells. This antiviral activity remains transient however, possibly as a consequence of degradation in intact cells. Since (2'-5')(A)n and its derivatives do not easily cross cell membranes, their possible use in antiviral chemotherapy is tightly linked with the development of vectors suitable for their administration in vivo.
D000227:Adenine Nucleotides / Q000378:metabolism* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D005988:Glyceric Acids / Q000378:metabolism*; D009841:Oligonucleotides / Q000378:metabolism* / Q000494:pharmacology*; D009843:Oligoribonucleotides / Q000378:metabolism* / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D012266:Ribose; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D000227:Adenine Nucleotides; D000998:Antiviral Agents; D005988:Glyceric Acids; D009841:Oligonucleotides; D009843:Oligoribonucleotides; C008885:2-phosphoglycerate; C023505:2',5'-oligoadenylate; D012266:Ribose; D010744:Phosphoric Monoester Hydrolases; D010727:Phosphoric Diester Hydrolases