Interactions of sulfur-containing acridine ligands with DNA by ESI-MS

Abstract

The alkylating proficiency of sulfur-containing mustards may be increased by using an acridine moiety to guide the sulfur mustard to its cellular target. In this study, the interactions of a new series of sulfur-containing acridine ligands, some that also function as alkylating mustards, with DNA were evaluated by electrospray ionization mass spectrometry (ESI-MS). Relative binding affinities were estimated from the ESI-MS data based on the fraction of bound DNA for DNA/acridine mixtures. The extent of binding observed for the series of sulfur-containing acridines was similar, presumably because the intercalating acridine moiety was identical. Upon infrared multi-photon dissociation (IRMPD) of the resulting oligonucleotide/sulfur-containing acridine complexes, ejection of the ligand was the dominant pathway for most of the complexes. However, for AS4, an acridine sulfide mustard, and AN1, an acridine nitrogen mustard, strand separation with the ligand remaining on one of the single strands was observed. At higher irradiation times, a variety of sequence ions were observed, some retaining the AS4/AN1 ligand, which was indicative of covalent binding.