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

Dale L Ang; Celine Kelso; Jennifer L Beck; Stephen F Ralph; David G Harman; Janice R Aldrich-Wright

doi:10.1007/s00775-020-01773-4

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

J Biol Inorg Chem. 2020 May;25(3):429-440. doi: 10.1007/s00775-020-01773-4. Epub 2020 Mar 26.

Authors

Dale L Ang¹, Celine Kelso², Jennifer L Beck², Stephen F Ralph², David G Harman³, Janice R Aldrich-Wright^{4

5}

Affiliations

¹ Nanoscale Organisation and Dynamics Group, School of Science, Western Sydney University, Penrith, NSW, 2751, Australia.
² School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong, 2522, Australia.
³ School of Medicine, Western Sydney University, Locked Bag 1797, Penrith South DC, NSW, 2751, Australia.
⁴ Nanoscale Organisation and Dynamics Group, School of Science, Western Sydney University, Penrith, NSW, 2751, Australia. j.aldrich-wright@westernsydney.edu.au.
⁵ School of Medicine, Western Sydney University, Locked Bag 1797, Penrith South DC, NSW, 2751, Australia. j.aldrich-wright@westernsydney.edu.au.

PMID: 32219553
DOI: 10.1007/s00775-020-01773-4

Abstract

The binding interactions of a series of square-planar platinum(II)-phenanthroline complexes of the type [Pt(P_L)(A_L)]²⁺ [where P_L = variously methyl-substituted 1,10-phenanthroline (phen) and A_L = 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.

Keywords: Anticancer drug; Binding affinity; Computational chemistry; Docking; G-quadruplex; Mass spectrometry; Platinum.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Circular Dichroism
Coordination Complexes / chemistry*
DNA / chemistry*
DNA / isolation & purification
Density Functional Theory*
G-Quadruplexes
Molecular Docking Simulation*
Molecular Structure
Phenanthrolines / chemistry*
Platinum / chemistry*
Spectrometry, Mass, Electrospray Ionization

Substances

Coordination Complexes
Phenanthrolines
Platinum
DNA