Lowering the overall charge on TMPyP4 improves its selectivity for G-quadruplex DNA.

Ligands that stabilize non-canonical DNA structures called G-quadruplexes (GQs) might have applications in medicine as anti-cancer agents, due to the involvement of GQ DNA in a variety of cancer-related biological processes. Five derivatives of 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4), where a N-methylpyridyl group was replaced with phenyl (4P3), 4-aminophenyl (PN3M), 4-phenylamidoproline (PL3M), or 4-carboxyphenyl (PC3M and P2C2M) were investigated for their interactions with human telomeric DNA (Tel22) using fluorescence resonance energy transfer (FRET) assay, and UV-visible and circular dichroism spectroscopies in K buffer. The molecules are cationic or zwitterionic with an overall charge of 3+ (4P3, PN3M, and PL3M), 2+ (PC3M) or neutral (P2C2M).