5'-dephosphorylated 2',5'-adenylate trimer and its analogs. Inhibition of tobacco mosaic virus replication in tobacco mosaic virus-infected leaf discs, protoplasts, and intact tobacco plants.
The effect of the 5'-dephosphorylated 2',5'-adenylate trimer and its 2',5'-trimer core analogs on the inhibition of tobacco mosaic virus (TMV) replication was determined in tobacco leaf discs, protoplasts, and whole tobacco plants, using infectivity tests and enzyme-linked immunosorbent assays. A structure-activity-metabolic stability-toxicity analysis of the 2',5'-adenylate trimer core molecule in TMV-infected Nicotiana glutinosa was determined. Modification at either the 6-amino position of the adenylate residues (i.e. inosinate trimer core) or at the 2' terminus (i.e. A-A-ara-A or A-A-Tu) inhibited replication of TMV. Modification of the 3'-hydroxyl group of the adenylate residues to 3-deoxyribose (i.e. the 2',5'-cordycepin trimer core) inhibited TMV replication better than the 2',5'-adenylate trimer core molecule. With enzyme-linked immunosorbent assays, there was complete inhibition of TMV replication by 200 nM 2',5'-adenylate trimer core for 60 h and by 200 nM 2',5'-cordycepin trimer core for 96 h. The amount of 2',5'-oligonucleotides associated with the leaves was determined using 2',5'-[3H]cordycepin trimer core; 1 X 10(-12) mol/cm2 of plant leaves inhibited TMV replication by 99%. No 2',5'-phosphodiesterase activity was detected in TMV-infected and noninfected leaf extracts. Therefore, the 2',5'-trimer cores were potent inhibitors of TMV replication at nanomolar concentrations, i.e. at 1000-fold lower concentration than that required in mammalian systems.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002472:Cell Transformation, Viral / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D007700:Kinetics; D010944:Plants / Q000382:microbiology*; D010947:Plants, Toxic; D011523:Protoplasts / Q000382:microbiology; D013329:Structure-Activity Relationship; D014026:Nicotiana / Q000382:microbiology; D014027:Tobacco Mosaic Virus / Q000187:drug effects / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects*
D000241:Adenosine