Phosphate-methylated DNA aimed at HIV-1 RNA loops and integrated DNA inhibits viral infectivity.
Phosphate-methylated DNA hybridizes strongly and specifically to natural DNA and RNA. Hybridization to single-stranded and double-stranded DNA leads to site-selective blocking of replication and transcription. Phosphate-methylated DNA was used to interrupt the life cycle of the human immunodeficiency virus type-1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Both antisense and sense phosphate-methylated DNA 20-nucleotide oligomers, targeted at the transactivator responsive region and the primer binding site, caused complete inhibition of viral infectivity at a low concentration. Hybridization of phosphate-methylated DNA with folded and unfolded RNA was studied by ultraviolet and proton nuclear magnetic resonance spectroscopy. The combined results of hybridization studies and biological experiments suggest that the design of effective antisense phosphate-methylated DNA should focus on hairpin loop structures in the viral RNA. For sense systems, the 5' end of the integrated viral genome is considered to be the important target site.
Buck
H M
HM
Department of Organic Chemistry, Eindhoven University of Technology, The Netherlands.
Koole
L H
LH
van Genderen
M H
MH
Smit
L
L
Geelen
J L
JL
Jurriaans
S
S
Goudsmit
J
J
D000926:Anticodon / Q000235:genetics; D001482:Base Composition; D001483:Base Sequence; D002460:Cell Line; D003062:Codon / Q000235:genetics; D015342:DNA Probes / Q000378:metabolism; D004279:DNA, Viral / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D008745:Methylation; D008961:Models, Structural; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009943:Organophosphorus Compounds / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics*; D013816:Thermodynamics; D014774:Virulence / Q000235:genetics
D000926:Anticodon; D003062:Codon; D015342:DNA Probes; D004279:DNA, Viral; D007202:Indicators and Reagents; D009943:Organophosphorus Compounds; D012367:RNA, Viral