Synthesis and crystallographic analysis of short pyridine based oligoamides as DNA targeting supramolecular binders

Thorfinnur Gunnlaugsson (1) , Daniel Omar Frimannsson (1) , Thomas Mccabe (1) , Mark Lawler (2)

1 School of Biochemistry and Immunology
2 School of Medicine, Institute of Molecular Medicine, St. James's Hospital

The synthesis of the pyridine peptides 1-4, formed from amino picolinic acid, and 5, made from coupling of a mono-protected pyridine diamine to a mono protected pyridine di-carboxylic acid and the X-ray crystallographic structures of 1 and 5 is discussed, as well as their supramolecular interactions in the solid state. The structure of these showed that they possess concave appearance that can be employed to bind to nucleic acids through multiple hydrogen-bonding, which would facilitate the formation of helical based pyridine oligoamides as novel DNA binding molecules. This was proven by carrying out DNA denaturatioin studies and ethididinium displacement assay on 5, but 5 was also shown using MTT assays to be cytotoxic against drug resistant chronic myeloid leukemia K562 cell-line.

Mots clés: Physical Sciences

Thorfinnur Gunnlaugsson, Daniel Omar Frimannsson, Thomas Mccabe, Mark Lawler. Synthesis and crystallographic analysis of short pyridine based oligoamides as DNA targeting supramolecular binders. Supramolecular Chemistry, 2010, 22 (9), pp.483. ⟨10.1080/10610278.2010.483732⟩. ⟨hal-00602606⟩