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.
Hamma
Tomoko
T
Department of Biochemistry and Molecular Biology, Johns Hopkins University, 615 North Wolfe St., Baltimore, MD 21205, USA.
Saleh
Anthony
A
Huq
Ikramul
I
Rana
Tariq M
TM
Miller
Paul S
PS
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