Fluorescent Oligonucleotide Probes for Screening High‐Affinity Nucleobase Surrogates

Abstract

Double-helical oligonucleotide probes featuring a single-nucleotide gap opposed by one of the canonical nucleobases and flanked by the fluorescent nucleobase analogue pyrrolocytosine have been synthesized and titrated with Pd chelates of dipicolinamide and its N ,N -dialkylated derivatives. The fluorometric titrations revealed greatly increased affinity of the Pd chelates for the nucleobases opposing the gap compared to the respective free nucleotides in solution. Owing to the constrained environment of the single-nucleotide gap, the relative stabilities of the various Pd -mediated base pairs were also significantly different from those previously reported at monomer level.

Selective Formation of Pd‐DNA Hybrids Using Tailored Palladium‐Mediated Base Pairs: Towards Heteroleptic Pd‐DNA Systems

“…We employed specifically designed Pd II -coordination compounds endowed with a unique capability to bind nucleobases along ss-DNA through both coordinating bonds and Watson-Crick complementary hydrogen bonds. [13] While some previous studies focused on the interaction of Pd IIcoordination compounds with nucleobases at monomeric level [14][15][16] or at single-nucleotide gap in double helixes, [17] our strategy aims to precisely organize a continuous one-dimen-sional array of Pd II ions and ligands along specific ss-DNA sequences. It is noteworthy that these ligands can be customized to create Pd II complexes with tailored substituents, thereby enhancing their affinity for nucleobases and/or introducing enhanced functionalities.…”