Synthesis and evaluation of a conformationally constrained pyridazinone PNA-monomer for recognition of thymine in triple-helix structures.
A novel conformationally constrained pyridazinone E(ag)-base PNA-monomer 2 capable of binding thymine in a triplex motif was designed and synthesised. A bis-PNA with the E(ag)-base incorporated in the Hoogsteen strand was hybridised with a complementary DNA. Thermal stability studies revealed an increase in T(m) (4.3 degrees C per mod.) compared to a no-base unit, but showed no improvement over a previously described unconstrained analogue (E, 1). Surprisingly, no significant difference was found in the thermodynamic parameters (DeltaH degrees, DeltaS degrees and DeltaG degrees ) for PNA-DNA triplex formation involving 2 or the unconstrained analogue 1.
Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen ø, Denmark.
Anne Goldbech
AG
Olsen
Otto
O
Dahl
Peter E
PE
Nielsen
D004353:Drug Evaluation, Preclinical / Q000379:methods; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000235:genetics; D011724:Pyridazines / Q000737:chemistry*; D013816:Thermodynamics; D013941:Thymine / Q000737:chemistry*
D020135:Peptide Nucleic Acids; D011724:Pyridazines; D013941:Thymine