A study of Pt(II)–phenanthroline complex interactions with double-stranded and G-quadruplex DNA by ESI–MS, circular dichroism, and computational docking

• DOI: 10.1007/s00775-020-01773-4
• Publication Date: 2020-03-26T12:03:05Z
• Authors: Dale L. Ang; Celine Kelso; Jennifer L. Beck; Stephen F. Ralph; David G. Harman; Janice R. Aldrich...
• Keywords: 0301 basic medicine; Spectrometry, Mass, Electrospray Ionization; Molecular Structure; Circular Dichroism; DNA; G-Quadruplexes; Molecular Docking Simulation; 03 medical and health sciences; Coordination Complexes; XXXXXX - Unknown; antineoplastic agents; platinum; Density Functional Theory; mass spectrometry; Phenanthrolines; Platinum

The binding interactions of a series of square-planar platinum(II)-phenanthroline complexes of the type [Pt(PL)(AL)]2+ [where PL = variously methyl-substituted 1,10-phenanthroline (phen) and AL = ethane-1,2-diamine (en)] were assessed with a G-quadruplex DNA (5'-TTG GGG GT-3', G4DNA) and a double-stranded DNA (5'-CGC GAA TTC GCG-3', dsDNA) sequence by ESI-MS. The results indicate a strong correlation between G4DNA affinity and increasing phenanthroline methyl substitution. Circular dichroism (CD) spectroscopy and molecular docking studies also support the finding that increased substitution of the phenanthroline ligand increased selectivity for G4DNA. ESI-MS was used to probe the interaction of a range of square-planar Pt(II)-phenanthroline complexes with double-stranded and G-quadruplex DNA.