Evaluation of binding selectivities and affinities of platinum-based quadruplex interactive complexes by electrospray ionization mass spectrometry

✍ Scribed by Sarah E. Pierce; Roxanne Kieltyka; Hanadi F. Sleiman; Jennifer S. Brodbelt

• Publisher: Wiley (John Wiley & Sons)
• Year: 2009
• Tongue: English
• Weight: 284 KB
• Volume: 91
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.21130

✦ Synopsis

Abstract

The quadruplex binding affinities and selectivities of two large π‐surface Pt^II^ phenanthroimidazole complexes, as well as a smaller π‐surface platinum bipyridine complex and a larger Ru^II^ complex, were evaluated by electrospray ionization mass spectrometry. Circular dichroism (CD) spectroscopy was used to determine the structures of various quadruplexes and to study the thermal denaturation of the quadruplexes in the absence and presence of the metal complexes. In addition, chemical probe reactions with glyoxal were used to monitor the changes in the quadruplex conformation because of association with the complexes. The platinum phenanthroimidazole complexes show increased affinity for several of the quadruplexes with elongated loops between guanine repeats. Quadruplexes with shorter loops exhibited insubstantial binding to the transition metal complexes. Similarly binding to duplex and single strand oligonucleotides was low overall. Although the ruthenium‐based metal complex showed somewhat enhanced quadruplex binding, the Pt^II^ complexes had higher quadruplex affinities and selectivities that are attributed to their square planar geometries. The chemical probe reactions using glyoxal indicated increased reactivity when the platinum phenanthroimidazole complexes were bound to the quadruplexes, thus suggesting a conformational change that alters guanine accessibility. © 2008 Wiley Periodicals, Inc. Biopolymers 91: 233–243, 2009.

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