High physiological thermal triplex stability optimization of twisted intercalating nucleic acids (TINA).
The structure of the monomer (R)-1-O-[4-(1-pyrenylethynyl)phenylmethyl]glycerol () in twisted intercalating nucleic acids (TINA) was optimized for stabilizing interactions between the intercalator and surrounding nucleobases when used as a triplex forming oligonucleotide (TFO). Enhancement of pi-pi interactions with nucleobases of the TFO was achieved by increasing the aromatic surface using the (R)-1-O-[4-(1-pyrenylethynyl)naphthylmethyl]glycerol monomer (). Bulge insertion of in the middle of a Hoogsteen-type triplex increased the triplex thermal stability, DeltaT(m) = +2.0 degrees C compared with at pH 7.2. Syntheses and thermal denaturation studies of triplexes and duplexes are described for three novel TINA monomers. The influence of pi-pi interactions, link length and the positioning of the ether in the linker in the TINA derivatives are described.
Bomholt
Niels
N
Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230, Odense M, Denmark.
Osman
Amany M A
AM
Pedersen
Erik B
EB
D000577:Amides / Q000737:chemistry; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005990:Glycerol / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009691:Nucleic Acid Denaturation; D063088:Phosphoramides; D010756:Phosphoric Acids / Q000737:chemistry; D044366:Transition Temperature
D000577:Amides; D007364:Intercalating Agents; D063088:Phosphoramides; D010756:Phosphoric Acids; C051802:triplex DNA; C005438:phosphoramide; D004247:DNA; D005990:Glycerol