This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, D.-S.
Right arrow Articles by Bae, Y.-S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, D.-S.
Right arrow Articles by Bae, Y.-S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2005, p. 4110-4120, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4110-4120.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Newly Designed Six-Membered Azasugar Nucleotide-Containing Phosphorothioate Oligonucleotides as Potent Human Immunodeficiency Virus Type 1 Inhibitors

Dong-Seong Lee,1 Kyeong-Eun Jung,2 Cheol-Hee Yoon,1 Hong Lim,2 and Yong-Soo Bae1*

Department of Biological Science, Sungkyunkwan University, Suwon, Gyounggi-do, South Korea,1 AgroPharma Research Institute, Dongbu Hannong Chemical Co., Daejeon, South Korea2

Received 22 January 2005/ Returned for modification 7 April 2005/ Accepted 7 July 2005

A series of modified oligonucleotides (ONs), characterized by a phosphorothioate (P{cjs0808}S) backbone and a six-membered azasugar (6-AZS) as a sugar substitute in a nucleotide, were newly synthesized and assessed for their ability to inhibit human immunodeficiency virus type 1 (HIV-1) via simple treatment of HIV-1-infected cultures, without any transfection process. While unmodified P{cjs0808}S ONs exhibited only minor anti-HIV-1 activity, the six-membered azasugar nucleotide (6-AZN)-containing P{cjs0808}S oligonucleotides (AZPSONs) exhibited remarkable antiviral activity against HIV-1/simian-human immunodeficiency virus (SHIV) replication and syncytium formation (50% effective concentration = 0.02 to 0.2 µM). The AZPSONs exhibited little cytotoxicity at concentrations of up to 100 µM. DBM 2198, one of the most effective AZPSONs, exhibited antiviral activity against a broad spectrum of HIV-1, including T-cell-tropic, monotropic, and even drug-resistant HIV-1 variants. The anti-HIV-1 activities of DBM 2198 were similarly maintained in HIV-1-infected cultures of peripheral blood mononuclear cells. When we treated severely infected cultures with DBM 2198, syncytia disappeared completely within 2 days. Taken together, our results indicate that DBM 2198 and other AZPSONs may prove useful in the further development of safe and effective AIDS-therapeutic drugs against a broad spectrum of HIV-1 variants.

* Corresponding author. Mailing address: Department of Biological Science, Sungkyunkwan University, Cheoncheon-dong 300, Jangan-gu, Suwon, Gyounggi-do 446-740, South Korea. Phone: (82)-31-290-5911. Fax: (82)-31-290-7087. E-mail: ysbae04{at}skku.edu.

Antimicrobial Agents and Chemotherapy, October 2005, p. 4110-4120, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4110-4120.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»