Synthesis of cationic glyco-oligoamide for DNA-carbohydrate interaction studies

Abstract

We are using carbohydrate-based ligands, glyco-oligoamides, as a strategy to obtain structural and thermodynamic information on carbohydrate-minor groove DNA binding. In order to improve the solubility of the first generation of neutral ligands type 1 in aqueous solution and the stability of the complexes formed with DNA as well as their sequence selectivity towards AT/TA base pairs, a new cationic vector β-d-Xyl-Py-γ[3(R)NH3 +]-Py-Ind 2 has been designed. Here, we present an efficient convergent solution-phase synthesis of the xylose cationic glyco-oligoamide 2, evidence of improvement of water solubility and the binding to polymers of DNA when compared with the xylose neutral ligand 1. This synthetic work paves the way to the synthesis of glyco-oligoamides with carbohydrates which contain in their structure cooperative hydrogen bonding centres based on our previous studies on carbohydrate cooperativity in apolar media and the use of the new design to achieve multivalency with calixaren-based platforms. © 2013 © 2013 Taylor & Francis.