DNA TRIPLE-HELIX STABILIZATION BY BISGUANIDINYL ANALOGS OF BIOGENIC POLYAMINES

The polycationic nature of biogenic polyamines such as spermine (SPM, 1) and spermidine (SPD, 2) plays an important role in selective bindin g to polyanionic nucleic acids. These interactions are mediated by ele ctrostatic 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 t o amplify the electrostatic component resulting in improved binding. A n easy chemical transformation route as described here gives rise to b isguanidinated derivatives of spermine (SPMG, 3) and spermidine (SPDG, 4). Both enhances DNA duplex stability over the parent polyamines whe reas 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. (C) 1996 Academic Press, Inc.