Synthesis of adenylyl-(3'----5')-guanosine and some analogues as probes to explore the molecular mechanism of stimulation of influenza virus RNA polymerase.
Influenza virus mRNA synthesis is primed by a capped oligonucleotide which is cleaved off from a cellular mRNA by a viral protein. The dinucleotide A3'p5'G can be used as a primer for the viral RNA polymerase mediated RNA synthesis in a cell-free system. Analogues of A3'p5'G have therefore been synthesized using the phosphotriester approach, and their priming ability for the influenza virus mRNA synthesis has been determined. An absence of the 2'-hydroxyl function in the guanosine residue in the dinucleotide, as in A3'p5'dG, drastically decreased its priming ability. Similarly, an alteration of the 3'----5' phosphate linkage to a 2'----5' phosphodiester linkage affected the priming ability quite severely. However a dinucleotide, with the 2'-hydroxyl function omitted in the adenosine moiety, as in dA3'p5'G, could still stimulate the mRNA synthesis. None of the modified dinucleotides inhibited A3'p5'G or globin mRNA primed influenza mRNA synthesis.
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000818:Animals; D002417:Cattle; D002474:Cell-Free System; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D015226:Dinucleoside Phosphates; D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D007202:Indicators and Reagents; D009980:Influenza A virus / Q000201:enzymology*; D009981:Influenza B virus / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D015226:Dinucleoside Phosphates; D007202:Indicators and Reagents; D012333:RNA, Messenger; D006151:Guanosine; C031924:adenylyl-(3'-5')-guanosine; D000249:Adenosine Monophosphate; D012321:DNA-Directed RNA Polymerases