Inhibition of human immunodeficiency virus type 1 activity in vitro by a new self-stabilized oligonucleotide with guanosine-thymidine quadruplex motifs.
An oligonucleotide with a dimeric hairpin guanosine quadruplex (basket type structure) (dG3T4G3-s), containing phosphorothioate groups, was able to inhibit human immunodeficiency virus type 1 (HIV-1)-induced syncytium formation and virus production (as measured by p24 core antigen expression) in peripheral blood mononuclear cells. This oligonucleotide lacks primary sequence homology with the complementary (antisense) sequences to the HIV-1 genome. Furthermore, this oligonucleotide may have increased nuclease resistance. The activity of this oligonucleotide was increased when the phosphodiester backbone was replaced with a phosphorothioate backbone. In vivo results showed that dG3T4G3-s was capable of blocking the interaction between gp120 and CD4. We also found that dG3T4G3-s specifically inhibits the entry of T-cell line-tropic HIV-1 into cells. This compound is a viable candidate for evaluation as a therapeutic agent against HIV-1 in humans.
Suzuki
Jun-ichiro
J
Department of Industrial Chemistry, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
Miyano-Kurosaki
Naoko
N
Kuwasaki
Tomoyuki
T
Takeuchi
Hiroaki
H
Kawai
Gota
G
Takaku
Hiroshi
H
D015726:Giant Cells / Q000187:drug effects; D006151:Guanosine / Q000737:chemistry; D016655:HIV Core Protein p24 / Q000187:drug effects; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D009841:Oligonucleotides / Q000737:chemistry* / Q000494:pharmacology*; D010710:Phosphates / Q000737:chemistry; D013936:Thymidine / Q000737:chemistry
D016655:HIV Core Protein p24; D009841:Oligonucleotides; D010710:Phosphates; D006151:Guanosine; C083120:phosphorodithioic acid; D013936:Thymidine