A comparative study of the interactions of cationic hetarenes with quadruplex-DNA forming oligonucleotide sequences of the insulin-linked polymorphic region (ILPR)

Abstract

The interactions of the ILPR sequence (ILPR = "insulin-linked polymorphic region") a2 [d(ACAG4TGTG4ACAG4TGTG4)] with [2.2.2]heptamethinecyanine derivatives 1a-e and with the already established quadruplex ligands coralyne (2), 3,3'-[2,6-pyridinediylbis(carbonylimino)]bis[1-methylquinolinium] (3), 4,4',4'',4'''-(21H,23H-porphine-5,10,15,20-tetrayl)tetrakis[1-methylpyridinium] (4), naphtho[2,1-b:3,4-b':6,5-b'':7,8-b''']tetraquinolizinium (5) and thiazole orange (6) were studied. It is demonstrated with absorption, fluorescence and CD spectroscopy that all investigated ligands bind with relatively high affinity to the ILPR-quadruplex DNA a2 (0.2-5.5 × 10(6) M(-1)) and that in most cases the binding parameters of ligand-ILPR complexes are different from the ones observed with other native quadruplex-forming DNA sequences.