title: Replacement of the ribofuranose oxygen of 2-5A derivatives by methylene: synthesis of an aristeromycin analogue of 2-5A core 5'-monophosphate (5'-O-phosphoryladenylyl)(2'----5')adenyl(2'----5')adenosine.
abstract: The ribofuranose oxygens of the three adenosine residues of the 5'-monophosphate of the 2-5A core [adenylyl(2'----5')adenylyl(2'----5')adenosine] were replaced by methylenes through the synthesis of an aristeromycin [9-[(1R,2S,3R,4R)-2,3-dihydroxy-4-(hydroxymethyl)cyclopentyl]adenosine] analogue. In the synthetic approach, the chlorophosphite triester procedure was employed together with the use of dimethoxytrityl and tert-butyldimethylsilyl protecting groups. The final product 14 was bound to the 2-5A-dependent endonuclease of mouse, rabbit, or human cells 100-300 times less effectively than parent p5'A2'p5'A2'p5'A. In extracts of human Daudi cells where the monophosphate p5'A2'p5'A2'p5'A was able to effect ribosomal RNA cleavage at 2 X 10(-7) M, 14 required a concentration of 2 X 10(-5) M to bring about discernible rRNA cleavage.
authors.forename: H
authors.initials: H
authors.lastname: Sawai
authors.forename: K
authors.initials: K
authors.lastname: Lesiak
authors.forename: J
authors.initials: J
authors.lastname: Imai
authors.forename: P F
authors.initials: PF
authors.lastname: Torrence
mesh_terms: D000227:Adenine Nucleotides / Q000138:chemical synthesis / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D004720:Endonucleases / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007739:L Cells / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology; D051379:Mice; D009843:Oligoribonucleotides; D011817:Rabbits; D012156:Reticulocytes / Q000201:enzymology
chemical_list: D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; C030034:aristeromycin; C023505:2',5'-oligoadenylate; C031128:adenylyl-(2'-5')-adenylyl-(2'-5')adenosine; D004720:Endonucleases; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D000241:Adenosine