Stabilization of guanine quadruplex DNA by the binding of porphyrins with cationic side arms

Many aromatic ligands, including tetra-(N-methyl-4-pyridyl)porphyrin (TMPyP4), have been reported to bind and stabilize quadruplex structure of telomeric DNA. We synthesized novel quadruplex-interacting porphyrins with cationic pyridinium and trimethylammonium arms at para- or meta-position of all phenyl groups of tetratolyl porphyrin. An antiparallel quadruplex structure was found to be stabilized more greatly by the meta-isomers than by the para-isomers and well-studied TMPyP4, as revealed by the increase in melting temperature of the quadruplex. One mole equivalent of the isomers was sufficient to stabilize the quadruplex. From the results of absorption, induced circular dichroism, and fluorescence resonance energy transfer spectro-scopic methods the unique site for the porphyrin binding is suggested to be the external guanine tetrad or groove of the quadruplex. The cationic side arms played a key role in the stabilization of the quadruplex structure. (c) 2005 Elsevier Ltd. All rights reserved.