@article{990a69605ca111dea8de000ea68e967b,
title = "High-affinity triplex targeting of double stranded DNA using chemically modified peptide nucleic acid oligomers",
abstract = "While sequence-selective dsDNA targeting by triplex forming oligonucleotides has been studied extensively, only very little is known about the properties of PNA-dsDNA triplexes-mainly due to the competing invasion process. Here we show that when appropriately modified using pseudoisocytosine substitution, in combination with (oligo)lysine or 9-aminoacridine conjugation, homopyrimidine PNA oligomers bind complementary dsDNA targets via triplex formation with (sub)nanomolar affinities (at pH 7.2, 150 mM Na(+)). Binding affinity can be modulated more than 1000-fold by changes in pH, PNA oligomer length, PNA net charge and/or by substitution of pseudoisocytosine for cytosine, and conjugation of the DNA intercalator 9-aminoacridine. Furthermore, 9-aminoacridine conjugation also strongly enhanced triplex invasion. Specificity for the fully matched target versus one containing single centrally located mismatches was more than 150-fold. Together the data support the use of homopyrimidine PNAs as efficient and sequence selective tools in triplex targeting strategies under physiological relevant conditions.",
author = "Hansen, {Mads E} and Thomas Bentin and Nielsen, {Peter E}",
year = "2009",
doi = "10.1093/nar/gkp437",
language = "English",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
}