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Journal of Virology, March 2002, p. 3015-3022, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.3015-3022.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Inhibition of Human Immunodeficiency Virus Type 1 Activity In Vitro by a New Self-Stabilized Oligonucleotide with Guanosine-Thymidine Quadruplex Motifs

Jun-ichiro Suzuki,1 Naoko Miyano-Kurosaki,2 Tomoyuki Kuwasaki,1 Hiroaki Takeuchi,1,3 Gota Kawai,1,2 and Hiroshi Takaku1,2*

Department of Industrial Chemistry,1 High Technology Research Center, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016,2 Department of Virology, Tohoku University, School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan3

Received 2 August 2001/ Accepted 3 December 2001

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.

* Corresponding author. Mailing address: Department of Industrial Chemistry and High Technology Research Center, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan. Phone: 81-474-78-0407. Fax: 81-474-71-8764. E-mail: takaku{at}ic.it-chiba.ac.jp.

Journal of Virology, March 2002, p. 3015-3022, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.3015-3022.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lee, D.-S., Jung, K.-E., Yoon, C.-H., Lim, H., Bae, Y.-S. (2005). Newly Designed Six-Membered Azasugar Nucleotide-Containing Phosphorothioate Oligonucleotides as Potent Human Immunodeficiency Virus Type 1 Inhibitors. Antimicrob. Agents Chemother. 49: 4110-4120 [Abstract] [Full Text]  
  • Kuwasaki, T., Hatta, M., Takeuchi, H., Takaku, H. (2003). Inhibition of human immunodeficiency virus 1 replication in vitro by a self-stabilized oligonucleotide with 2'-O-methyl-guanosine-uridine quadruplex motifs. J Antimicrob Chemother 51: 813-819 [Abstract] [Full Text]  


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