Antiviral oligo- and polyribonucleotides containing selected triazolo[2,3-a]purines.
Several amphipathic (hydrophobic base, hydrophilic backbone) polyribonucleotides have recently been shown to have potent antiviral activity against HIV and human cytomegalovirus (HCMV). The working hypothesis developed during these studies was that the ability to form an ordered, non-hydrogen-bonded array in solution was an important criterion for activity. To explore further the role of structure and molecular size on the inhibition of virus replication, one new polynucleotide and two 32-mer oligonucleotides based on the triazolo[2,3-a]purine ring system have now been prepared. High-molecular-weight polynucleotide 4a (PTPR) and sulfur-containing 32-mer 5b (TTPR) were moderately active against HIV but showed greater potency against HDMV than ganciclovir. Both 4a and 5b gave clear evidence of cooperative melting behavior, whereas inactive 32-mer 5a showed no such behavior.
Tutonda
M G
MG
Department of Medicinal Chemistry, 20 South 2030 East, 295 Biomedical Polymers Research Building, University of Utah, Salt Lake City, Utah 84112-9453, USA.
Buckheit
R W
RW
Agrawal
V K
VK
Broom
A D
AD
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects / Q000254:growth & development; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011131:Polyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011687:Purines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D009843:Oligoribonucleotides; D011131:Polyribonucleotides; D011687:Purines; C116270:poly(5-methyl-9-oxo-3-ribofuranosyl-1,2,4-triazolo(2,3-a)purinylic acid); C116271:poly(5-methyl-9-thio-3-(2'-deoxy-2'-methoxyribofuranosyl)-1,2,4-triazolo(2,3-a)purinylic acid)