Bioorganic & Medicinal Chemistry Letters 2006-05-15

Zn2+ dependent DNA binders based on terminally modified peptide nucleic acids.

Iris Boll, Larisa Kovbasyuk, Roland Krämer, Thomas Oeser, Andriy Mokhir

Index: Bioorg. Med. Chem. Lett. 16(10) , 2781-5, (2006)

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Abstract

Two ligand-intercalator-peptide nucleic acid conjugates (L-NADI-PNAs) have been synthesized. Affinity of these conjugates to their complementary DNAs was found to be affected by Zn(2+). The magnitude of this effect could be controlled by a variation of the ligand. Upon binding Zn(2+) the L-NADI-PNAs form positively charged ZnL complexes, which interact with the negatively charged DNA backbone. This electrostatic interaction stabilizes PNA/DNA duplexes. It has been found that Zn(2+) dependent stabilization takes place only if the ZnL complex has a higher total positive charge than the ligand. Linear correlation has been observed between Zn(2+) induced stabilization of PNA/DNA duplexes and difference of charges of the ZnL complex and the ligand.