Specific Binding of a Hexanucleotide to Hiv-1 Reverse Transcriptase: a Novel Class of Bioactive Molecules.
From: Kompetenzzentrum Drug Design and Target Monitoring, Maria-Göppert-Strasse 1, D-23538 Lübeck, Germany.
Nucleic acids research
- Publish Date: 2006
- ISSN: 1362-4962
- Volume: 34
- Issue: 19
- Pages: 5631-7
- Medium: Internet
- Language: English
- Citation (JAMA): Mescalchin Alessandra, Wünsche Winfried, Laufer Sandra D, et al. Specific Binding of a Hexanucleotide to Hiv-1 Reverse Transcriptase: a Novel Class of Bioactive Molecules.. Nucleic Acids Res. 2006;34:5631-7
Abstract
Short oligonucleotides below 8-10 nt in length adopt relatively simple structures. Accordingly, they represent interesting and so far unexplored lead compounds as molecular tools and, potentially, for drug development as a rational improvement of efficacy seem to be less complex than for other classes of longer oligomeric nucleic acid. As a ‘proof of concept’, we describe the highly specific binding of the hexanucleotide UCGUGU (Hex-S3) to human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) as a model target. Ultraviolet (UV) cross-linking studies and competition experiments with primer/template substrates and a RT-directed aptamer suggest site-specific binding of Hex-S3 to the large subunit (p66) of the viral enzyme. The affinity of 5.3 muM is related to hexanucleotide-specific suppression of HIV-1 replication in human cells by up to three orders of magnitude indicating that Hex-S3 exerts specific and biologically relevant activity. Experimental evidence described here further suggests a systematic hexamer array-based search for new tools for molecular biology and novel lead compounds in nucleic acid-based drug development.
Mesh Headings (Keywords): Anti-HIV Agents, Binding Sites, Cell Line, Drug Design, Enzyme Inhibitors, HIV Reverse Transcriptase, HIV-1, Humans, Oligodeoxyribonucleotides, Oligonucleotide Array Sequence Analysis, Oligoribonucleotides, Transfection, Virus Replication
Check for Full Text / PubMed Unique Identifier (PMID): 17038335
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