Triple helical DNA formation by a hydrophobic oligonucleotide-peptide hybrid molecule

Abstract

Stable triple helical DNA formation with triplex forming oligonucleotide–peptide hybrids, containing hydrophobic peptides, has previously been difficult to achieve. We report hereon stable triplexation with an oligonucleotide–peptide hybrid containing a hydrophobic peptide. The peptide of interest is the gp41b peptide, which is derived from the hydrophobic terminal domain of the HIV transmembrane glycoprotein gp41. Triplex forming oligonucleotides conjugated to the gp41b peptide were prepared with and without intramolecular spacer linkers. Hybrids with appropriate spacers formed stable triplexes whereas those without the linkers did not. Oligonucleotide–peptide conjugates have several applications mainly in control of gene expression, with the peptide enhancing intracellular delivery of the oligonucleotide. The gp41b peptide is one of a number of candidate peptides considered to be potential delivery vectors. Hence, the data presented here may prove to be useful in designing such conjugates. Our data also extend the list of DNA structures known to stabilize triplexes and suggest that triplexation by oligonucleotide–peptide hybrids may be peptide sequence dependent.