Induction of helical handedness and DNA binding properties of peptide nucleic acids (PNAs) with two stereogenic centres

A systematic study on the combined effects of two lysine-derived stereogenic centres at C2 and C5 of a PNA monomer inserted within an achiral PNA strand was performed by circular dichroism, UV spectroscopy and ESI mass spectrometry by taking into account all four diastereomers. The stereogenic centres induced different preferential helix handednesses in the PNA strands, which in turn affected their ability to bind to the complementary DNA. The helical induction, studied on the PNA-PNA duplexes, evidenced that in the case of "chiral conflict" (induction of opposite helices), the stereogenic centre at C5 was clearly prevalent in determining the preferential helix handedness. The PNA-DNA duplex stability was found to be related to the number and the position of the stereogenic centres inducing a preference for a right-handed helix, as well as with the strength of the helical induction. Thermodynamic parameters evaluated by the Van't Hoff model clearly outlined the different enthalpic and entropic contributions of the substitutions at C2 and C5. These findings expand the knowledge of the role of punctual stereogenic centres in inducing supramolecular chirality in PNAs, demonstrate the ability of right-handed DNA to act as a chiral selector and are essential for the future design of chiral PNAs with improved DNA affinity. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)