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.
Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230, Odense M, Denmark.
Niels
N
Bomholt
Amany M A
AM
Osman
Erik B
EB
Pedersen
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