The Thermodynamic Effects of Ligand Structure on the Molecular Recognition of Mono‐ and Biruthenium Polypyridyl Complexes with G‐Quadruplex DNA

Autor: Frederick M. MacDonnell, J. Cole Gwin, Logan R. Martin, Jake C. White, Nagham Alatrash, Savannah J. West, Clinton G. Mikek, Carmen Shumaker, Edwin A. Lewis, Venkata R. Machha, Arseniy Butrin
Rok vydání: 2017
Předmět:
Zdroj: European Journal of Inorganic Chemistry. 2017:3953-3960
ISSN: 1099-0682
1434-1948
DOI: 10.1002/ejic.201700789
Popis: ITC and CD were used to study the thermodynamics of RPC*G-quadruplex DNA (G4) complex formation. RPCs were [Ru(phen)₃]²+ (1²+), [Ru(phen)₂(dppz)]²+ (2²+), [Ru(phen)₂(tatpp)]²+ (3²+), and [Ru(phen)₂(tatpp)(phen)₂Ru]⁴+ (4⁴+) and target DNAs were c-MYC NHE-III1 promoter sequence mutants forming 1-2-1 and 1-6-1 G-quadruplexes. Formation of the 2:1 RPC*G4 complexes is characterized by entropy driven RPC binding to the top and bottom of G-tetrad faces. 1²+ appears to bind very weakly or not at all to G4 DNA. 2²+ having a dipyridophenazine group to stack on the top and bottom of the G4 core, exhibits an average Ka = 6.7 x 10⁴ M-¹. 3²+, with a larger G4 interactive tetraazatetrapyrido-pentacene group, binds with significantly higher affinity, Ka = 1.1 x 10⁶ M-¹. 2²+ and 3²+ appear to bind independently of G4 folding topology and RPC conformation. The thermograms for the titration of G4 DNA with rac-4⁴+ are characterized by two binding modes exhibiting higher and lower affinity (Ka,1 = 3.6 x 10⁷ M-1 and Ka,2 = 3.2 x 10⁵ M-1). The two binding modes are attributed to preferential binding of one of the 4⁴+ enantiomers (e.g. ΛΛ) over the other isomers (e.g. ΔΔ or ΔΛ). Tighter binding of the preferred 4⁴+ enantiomer, in comparison to 3²+, is due to additional favorable entropy for locating a second [(phen)₃Ru-]²+ moiety in a G4 groove. Weaker binding of the disfavored 4⁴+ isomers must be due to a poorer fit of these isomers with the G4 faces.
Databáze: OpenAIRE
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