Interactions of ruthenium(II) polypyridyl complexes with human telomeric DNA

Vienna T Tran; Joshua Turek-Herman; Michelle Ferreira; Kailey N Martin; Dana Beseiso; Benjamin R Williams; Frederic Rosu; Valérie Gabelica; Sharon J Nieter Burgmayer; Liliya A Yatsunyk

doi:10.1016/j.jinorgbio.2023.112388

Interactions of ruthenium(II) polypyridyl complexes with human telomeric DNA

J Inorg Biochem. 2023 Dec:249:112388. doi: 10.1016/j.jinorgbio.2023.112388. Epub 2023 Sep 26.

Authors

Affiliations

¹ Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave., Swarthmore, PA, USA. Electronic address: vietran@uw.edu.
² Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave., Swarthmore, PA, USA. Electronic address: joshuart@princeton.edu.
³ Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave., Swarthmore, PA, USA. Electronic address: michelle.ferreira@duke.edu.
⁴ Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave., Swarthmore, PA, USA. Electronic address: kailey.martin33@gmail.com.
⁵ Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave., Swarthmore, PA, USA. Electronic address: dbeseiso@umich.edu.
⁶ Department of Chemistry, Bryn Mawr College, Bryn Mawr, PA 19010, USA. Electronic address: benjamin.williams@northwestern.edu.
⁷ Univ. Bordeaux, CNRS, INSERM, IECB, UAR3033, US01, F-33600 Pessac, France. Electronic address: frederic.rosu@u-bordeaux.frv.
⁸ Univ. Bordeaux, CNRS, INSERM, IECB, UAR3033, US01, F-33600 Pessac, France; Univ. Bordeaux, CNRS, INSERM, ARNA, UMR5320, U1212, IECB, F-33600 Pessac, France. Electronic address: v.gabelica@iecb.u-bordeaux.fr.
⁹ Department of Chemistry, Bryn Mawr College, Bryn Mawr, PA 19010, USA. Electronic address: sburgmay@brynmawr.edu.
¹⁰ Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave., Swarthmore, PA, USA. Electronic address: lyatsun1@swarthmore.edu.

PMID: 37837940
PMCID: PMC10668861 (available on 2024-12-01)
DOI: 10.1016/j.jinorgbio.2023.112388

Abstract

Eight [Ru(bpy)₂L]²⁺ and three [Ru(phen)₂L]²⁺complexes (where bpy = 2,2'-bipyridine and phen = 1,10-phenanthroline are ancillary ligands, and L = a polypyridyl experimental ligand) were investigated for their G-quadruplex binding abilities. Fluorescence resonance energy transfer melting assays were used to screen these complexes for their ability to selectively stabilize human telomeric DNA variant, Tel22. The best G-quadruplex stabilizers were further characterized for their binding properties (binding constant and stoichiometry) using UV-vis, fluorescence spectroscopy, and mass spectrometry. The ligands' ability to alter the structure of Tel22 was determined via circular dichroism and PAGE studies. We identified me₂allox as the experimental ligand capable of conferring excellent stabilizing ability and good selectivity to polypyridyl Ru(II) complexes. Replacing bpy by phen did not significantly impact interactions with Tel22, suggesting that binding involves mostly the experimental ligand. However, using a particular ancillary ligand can help fine-tune G-quadruplex-binding properties of Ru(II) complexes. Finally, the fluorescence "light switch" behavior of all Ru(II) complexes in the presence of Tel22 G-quadruplex was explored. All Ru(II) complexes displayed "light switch" properties, especially [Ru(bpy)₂(diamino)]²⁺, [Ru(bpy)₂(dppz)]²⁺, and [Ru(bpy)₂(aap)]²⁺. Current work sheds light on how Ru(II) polypyridyl complexes interact with human telomeric DNA with possible application in cancer therapy or G-quadruplex sensing.

Keywords: FRET; G-quadruplex; Human telomeric DNA; Mass spectrometry; Ruthenium polypyridyl complexes; “Light switch” effect.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

DNA / chemistry
Fluorescence Resonance Energy Transfer
G-Quadruplexes*
Humans
Ligands
Ruthenium* / chemistry

Substances

Ruthenium
Ligands
DNA

Grants and funding

R15 CA253134/CA/NCI NIH HHS/United States