Inhibition of HIV tat-TAR interactions by an antisense oligo-2'-O-methylribonucleoside methylphosphonate.
An antisense oligo-2'-O-methylribonucleotide having alternating methylphosphonate/phosphodiester linkages, 1676, whose sequence is complementary to the apical stem-loop of HIV-1 TAR RNA, was prepared to determine its effects on Tat protein-TAR interaction and Tat-mediated gene transactivation in cell culture. This oligomer and its all-phosphodiester analogue, 1707, were shown to: (1) bind to TAR at 37 degrees C with K(d)'s in the low nM concentration range; (2) inhibit Tat-TAR complex formation; and (3) inhibit expression of a chloramphenicol reporter gene under control of the HIV LTR in HeLa HL3T1 cells in culture.
Department of Biochemistry and Molecular Biology, Johns Hopkins University, 615 North Wolfe St., Baltimore, MD 21205, USA.
Tomoko
T
Hamma
Anthony
A
Saleh
Ikramul
I
Huq
Tariq M
TM
Rana
Paul S
PS
Miller
D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D018075:RNA, Complementary / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D009943:Organophosphorus Compounds; D018075:RNA, Complementary; D012333:RNA, Messenger; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; C032627:methylphosphonic acid; D015500:Chloramphenicol O-Acetyltransferase