Antiviral amphipathic oligo- and polyribonucleotides: analogue development and biological studies.
A series of novel N1 alkylated purine nucleic acids were polymerized either enzymatically or by automated synthesis to further establish the SAR requirements for HIV, RT, and HCMV activity. Out of the series, two constructs, 2'-O-methyl-1-allylinosinic acid phosphorothioate 33-mer (16) and an oligomer incorporating 1-propyl-6-thioinosinic acid residues (20), were found to be highly active under all three assay conditions. SAR studies indicate that sulfur incorporation, high molecular weight, and low steric bulk at N1 all can be important for activity.
Department of Medicinal Chemistry, 201 Skaggs Hall, University of Utah, 30 South 2000 East, Salt Lake City, Utah 84112-5820, USA.
Robyn M
RM
Hyde
Arthur D
AD
Broom
Robert W
RW
Buckheit
D000498:Allyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival; D003587:Cytomegalovirus / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007291:Inosine Monophosphate / Q000737:chemistry; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers; D011119:Polynucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000498:Allyl Compounds; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D009843:Oligoribonucleotides; D011108:Polymers; D011119:Polynucleotides; D018894:Reverse Transcriptase Inhibitors; D013873:Thionucleotides; D007291:Inosine Monophosphate