Ojwang J, Buckheit R, Rando R; National Conference on Human Retroviruses and Related Infections.
Program Abstr Second Natl Conf Hum Retrovir Relat Infect Natl Conf Hum Retrovir Relat Infect 2nd 1995 Wash DC. 1995 Jan 29-Feb 2; 68.
Triplex Pharm. Corp., The Woodlands, TX.
Abstract: T30177 is an oligonucleotide with natural phosphodiester (PD) backbone composed of only deoxyguanosine and thymidine (GTO)). It is 17-nt in length and able to significantly inhibit human immunodeficiency virus type-1 (HIV) production in acute infection assays. This molecule has been synthesized with phosphorothioate 5' and 3' penultimate internucleoside linkages for stability. The oligonucleotide does not share any homology with, or posses any complementary (antisense) sequence motifs to the HIV-1 genome. T30177 inhibits replication of multiple laboratory isolates HIV-1 in human T-cell lines and in fresh human peripheral blood lymphocytes (PBLs). Variations in the multiplicity of infection (MOI) has very little effect on the IC50 value of T30177 as compared to AZT or DDI. The compound is also able to inhibit multiple clinical isolates of HIV-1 and prevents the cytopathic effect of the virus in primary CD4+ T-cells. The median inhibitory dose (IC50) is in the submicromolar range while the toxicity values are greater than 100 micromolar in PBLs which results in a high selective index. In addition, T30177 significantly suppresses HIV-1 p24 production at least 7 days after removal of the drug from the infected cell culture medium. Studies are currently underway to elucidate the mechanism(s) of action T30177. The antiviral activity shown for both laboratory and clinical isolates of HIV-1 T30177 in tissue culture and primary cells makes this compound a good candidate to warrant investigation as a therapeutic agent to be used against HIV-1.
Publication Types:
Keywords:
- Animals
- Antigens, CD4
- Antiviral Agents
- Base Sequence
- Deoxyguanosine
- HIV Infections
- HIV-1
- Humans
- Oligonucleotides
- Oligonucleotides, Antisense
- T 30177
- Thymidine
- genetics
- immunology
- reverse transcriptase, Human immunodeficiency virus 1
Other ID:
UI: 102213051
From Meeting Abstracts