Wang A, Wang JH; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1998 Sep 24-27; 38: 367 (abstract no. I-15).

Natural Sciences Center, State University of New York, Buffalo.

Irrespective of their nucleotide sequences, all poly-2'-0-(2,4-dinitrophenyl)-oligoribonucleotides (DNP-oligos) are potent, mutation-insensitive inhibitors of reverse transcriptases (RT). These amphipathic molecules are also bioavailable antiviral agents, since they are membrane-permeable and RNase-resistant. DNP-oligos with antisense sequences complementary to specific segments of the envelope and protease genes of MLV were synthesized as bifunctional and trifunctional inhibitors. Intraperitoneal administration of these inhibitors to leukemic mice for 3 weeks decreased viremia to undetectable le,vel by RT-PCR assay, with no virus rebound even 8 weeks after termination of the treatment when the mice were sacrificed for autopsy. All infected but untreated mice died in 6 months with enlarged spleens. The infected and subsequently treated mice stayed healthy with normal spleens, and no integrated viral genome was found in either their spleen or bone marrow by PCR assay. The observed effective intraperitoneal dosages (ED50) are 50, 0.25 and 0.1 mg/Kg for the monofunctional, bifunctional and trifunctional DNP-oligos respectively. These inhibitors are also effective by oral administration, but the effective dosages are 10-fold higher.

Publication Types:

• Meeting Abstracts

Keywords:

• 2,4-Dinitrophenol
• Animals
• Antiviral Agents
• Base Sequence
• Bone Marrow
• DNA Primers
• Dinitrobenzenes
• Humans
• Leukemia Virus, Murine
• Mice
• Moloney murine leukemia virus
• Oligoribonucleotides
• Oligoribonucleotides, Antisense
• Polymerase Chain Reaction
• RNA-Directed DNA Polymerase
• Reverse Transcriptase Polymerase Chain Reaction
• Spleen
• Viremia
• genetics

Other ID:

• 20710820

UI: 102188134

From Meeting Abstracts