The Ly Group

Bioorganic Chemistry  •  Combinatorial Chemistry  •  Chemical Genetics  •  Functional Genomics


DNA Recognition

One aspect of our work is focused on the design of modified peptide nucleic acid (PNA) for recognition of double-stranded B-form DNA (B-DNA), based on the simple rules of Watson-Crick base-pairing. Previously we have shown that PNA, when preorganized into a right-handed helix by installing an appropriate stereogenic center at the γ-backbone position, can invade any sequence of double-stranded B-DNA. However, with the recurrent design, this binding mode is limited to relatively low ionic strengths—due mainly to the lack of binding free energy. Current work is focused on the design of modified nucleobases with improved hydrogen-bonding and base-stacking capabilities and on the development of 'Janus' nucleobases that are capable of forming Watson-Crick hydrogen-bonding interactions with both strands of the DNA double helix, with the overall goal of being able to target any sequence of double-stranded B-DNA under physiological conditions based on the well-established rule of Watson-Crick base-pairing.