Backbone modified oligodeoxynucleotides: stereoselective synthesis of methylphosphonates and HIV inhibitory capacity of phosphorothioates.
Oligonucleotides bearing phosphorothioate linkages of the HIV tatIII splice acceptor site were synthesized by automated solid phase synthesis. Especially 5'- and 3'-end capped thioates of the sequence 5'-ACACCCAATTCTGAAAATGG-3' show microM inhibition of HIV replication. ODN-methylphosphonates of defined stereochemistry were obtained with suitably modified proline phosphonamidite derivatives as monomeric building blocks. Asymmetric induction for nucleosidephosphonamidates up to 5:1 (Rp:Sp rsp. Sp:Rp depending on configuration of proline-moiety) could be reached. The intermediate phosphonamidite can be further reacted to dinucleoside methylphosphonates of enriched diastereomeric excess.
Engels
J W
JW
Institut für Organische Chemie, Universität Frankfurt, FRG.
Daum
T
T
Frauendorf
A
A
Lüking
S
S
Mag
M
M
Müller
W E
WE
Muth
J
J
Rosmanitz
P
P
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001483:Base Sequence; D006678:HIV / Q000187:drug effects*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D063086:Organothiophosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides; D063065:Organophosphonates; D063086:Organothiophosphates