DNA binding of a D-lysine-based chiral PNA: Direction control and mismatchrecognition

Citation
S. Sforza et al., DNA binding of a D-lysine-based chiral PNA: Direction control and mismatchrecognition, EUR J ORG C, (16), 2000, pp. 2905-2913
Citations number
18
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Organic Chemistry/Polymer Science
Journal title
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
ISSN journal
1434-193X → ACNP
Issue
16
Year of publication
2000
Pages
2905 - 2913
Database
ISI
SICI code
1434-193X(200008):16<2905:DBOADC>2.0.ZU;2-Q
Abstract
Peptide nucleic acids (PNAs) are oligonueleotide analogues with a skeleton made up of N-(2-aminoethyl)glycine units; they bind to complementary DNA an d RNA with high stability and specificity. In order to improve the binding specificity, solubility and uptake into cells, many modifications have been introduced, some concerning the introduction of stereogenic centres. With the aim of achieving a selective antiparallel binding with DNA, we report i n this paper the synthesis and binding abilities of a chiral PNA decamer (H GTAGATCACT-NH2) bearing three D-Lys-based monomers (a "chiral box") in the middle of the strand. Indeed, the antiparallel PNA-DNA duplex showed a melt ing point of 43 degrees C (determined both by CD and UV spectroscopy), wher eas the parallel PNA-DNA duplex failed to form, as shown by the absence of temperature dependence in the UV and CD spectra. Moreover, hybridization ex periments carried out with antiparallel DNA strands bearing single mismatch es showed that this PNA was excellent in discriminating between mismatched and matched targets. These results indicate that a high chiral constraint i n the middle of a PNA sequence strongly affects the direction selectivity, i.e. the antiparallel/parallel preference in the DNA complexation. In parti cular, a "D-chiral box" favours a highly specific antiparallel DNA binding, thus allowing possible diagnostic applications for the screening of single -point mutations.