title: Inhibition of human immunodeficiency virus type 1 activity in vitro by a new self-stabilized oligonucleotide with guanosine-thymidine quadruplex motifs.
abstract: 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.
authors.affiliation: Department of Industrial Chemistry, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Suzuki
authors.forename: Naoko
authors.initials: N
authors.lastname: Miyano-Kurosaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kuwasaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Gota
authors.initials: G
authors.lastname: Kawai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaku
mesh_terms: 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
chemical_list: D016655:HIV Core Protein p24; D009841:Oligonucleotides; D010710:Phosphates; D006151:Guanosine; C083120:phosphorodithioic acid; D013936:Thymidine