DNA triple helix stabilization by bisguanidinyl analogues of biogenic polyamines

Abstract

The polycationic nature of biogenic polyamines such as spermine (SPM,1) and spermidine (SPD,2) plays an important role in selective binding to polyanionic nucleic acids. These interactions are mediated by electrostatic and hydrogen bonding forces which lead to stabilization of DNA duplexes and triplexes. Transformation of primary amino groups in these molecules into corresponding guanidinium functions is expected to amplify the electrostatic component resulting in improved binding. An easy chemical transformation route as described here gives rise to bisguanidinated derivatives of spermine (SPMG,3) and spermidine (SPDG,4). Both enhances DNA duplex stability over the parent polyamines whereas SPMG is more selective for stabilization of DNA triplexes even at pH 7.0. The results have implication for designing of new DNA binding ligands.