Versatile cyanine-click-amino acid conjugates showing one-atom-influenced recognition of DNA/RNA secondary structure and mitochondrial localization in living cells

May 22, 2018

Title

Versatile cyanine-click-amino acid conjugates showing one-atom-influenced recognition of DNA/RNA secondary structure and mitochondrial localization in living cells

Author

Tamara Smidlehner, Atanas Kurutos, Jakov Slade, Robert Belužić, Dale L. Ang, Alison Rodger, Ivo Piantanida

Year

2018

Journal

European Journal of Organic Chemistry

Abstract

By a simple click-CuAAC procedure several cyanine dye analogues were attached to the amino acid side chain, yielding chromophore-amino acid conjugates, with potential of fluorescence upon binding to target. Due to the amino acid C- and N-termini available for peptide coupling, these conjugates are suitable for easy incorporation into a peptide backbone. Moreover, "click" procedures also allow post-peptide synthesis attachment of the dye. Novel amino acid dyes, although intrinsically non-fluorescent, give rise to strong fluorimetric response upon binding to double-stranded (ds)-DNAs or ds-RNA, whereby selectivity in emission response to various polynucleotide secondary structures is controlled either by linker length or halogen atom located on the cyanine part of the molecule. Molecular modeling confirmed the mode of binding to different polynucleotides, which was responsible for recognition. Interestingly, cell localisation experiments show that the dyes were specifically localised in mitochondria at variance with the localisation of parent dyes, which accumulate in cell nuclei, pointing out that the amino acid tail (containing triazole ring) might function as a novel mitochondria-directing appendage

Instrument

J-815

Keywords

Circular dichroism, Induced circular dichroism, Linear dichroism, DNA structure, Ligand binding, Organic chemistry, Biochemistry