Azasugar Nucleotide-containing Phosphorothioate Oligonucleotides as an AIDS Therapeutic Drug.
- Author:
Dong Sung LEE
1
;
Hong LIM
;
Yong Soo BAE
Author Information
1. Department of Microbiology, Hannam University, Daejeon, Korea. ysbae@eve.hannam.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Azarsugar-containing P=S oligonucleotide (AZPSON);
HIV-1;
AZPSON-2198;
Therapeutic drug
- MeSH:
Giant Cells;
HIV;
HIV-1;
Nucleotides;
Oligonucleotides;
Phosphorothioate Oligonucleotides*
- From:Journal of Bacteriology and Virology
2002;32(2):165-176
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
A series of modified oligonucleotides containing P=S backbone and a six-membered azasugar (6-AZS) were synthesized and tested for their ability to inhibit human immunodeficiency virus (HIV) in vitro without the aid of any transfecting agents. While P=S oligonucleotides with natural nucleotides had little anti-HIV-1 activity, six-membered azasugar nucleotide (6-AZN)-containing P=S oligonucleotides (AZPSON) potently inhibited the HIV-1/SHIV production and syncytium formation in vitro (EC50 = 0.02~0.2 micro M) without cytotoxicity up to 100 micro M. AZPSONs are enzymatically stable over 6 days in culture supernatant. Phosphodiester (P=O) backbone only or mixed backbone (P=O and P=S) oligonucleotides that contain 6-AZN did not exhibit anti-HIV-1 activity. The anti-HIV-1 capacity of AZPSON seems to depend on the number and/or distribution patterns of 6-AZN in the oligonucleotides. The oligomer 2198, most effective for anti-HIV-1 activity among the AZPSONs, was much more effective than ddI or ddC in anti-HIV activity. Particularly noteworthy is that the anti-HIV-1 activity of AZPSON-2198 was better than AZT in the long-lasting efficacy after a single treatment.
