Specific binding of a hexanucleotide to HIV-1 reverse transcriptase: A novel class of bioactive molecules

Alessandra Mescalchin, Winfried Wünsche, Sandra D. Laufer, Dina Grohmann, Tobias Restle, Georg Sczakiel*

*Corresponding author for this work
7 Citations (Scopus)


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 μM 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.

Original languageEnglish
JournalNucleic Acids Research
Issue number19
Pages (from-to)5631-5637
Number of pages7
Publication statusPublished - 01.11.2006


Dive into the research topics of 'Specific binding of a hexanucleotide to HIV-1 reverse transcriptase: A novel class of bioactive molecules'. Together they form a unique fingerprint.

Cite this