Hybridization of Complementary and Homologous Peptide Nucleic Acid Oligomers to a Guanine Quadruplex-Forming RNA

摘要

Peptide nucleic acid (PNA) oligomers targeted to guanine quadruplex-forming RNAs can be designed in two different ways.First,complementary cytosine-rich PNAs can hybridize by the formation of Watson-Crick base pairs,resulting in hybrid PNA-RNA duplexes.Second,guanine-rich homologous PNAs can hybridize by the formation of G tetrads,resulting in hybrid PNA-RNA quadruplexes.UV thermal denaturation,circular dichroism,and fluorescence spectroscopy experiments were used to compare these two recognition modes and revealed 1:1 duplex formation for the complementary PNA and 2:1 (PNA_2-RNA) quadruplex formation for the homologous PNA.Both hybrids were very stable,and hybridization was observed at low nanomolar concentrations.Hybrid quadruplex formation was equally efficient regardless of the PNA strand polarity,indicating a lack of interaction between the loop nucleobases on the PNA and RNA strands.The implications of this finding on sequence specificity as well as methods to improve affinity are also discussed.