Thermodynamic Profiles and Nuclear Magnetic Resonance Studies of Oligonucleotide Duplexes Containing Single Diastereomeric Spiroiminodihydantoin Lesions

Autor:	Na Zhang, Nicholas E. Geacintov, Vladimir Shafirovich, Dinshaw J. Patel, Luis A. Marky, Irine Khutsishvili, Conor Crean
Rok vydání:	2013
Předmět:	Oligonucleotide Guanine Stereochemistry Guanosine Stereoisomerism Biochemistry Molecular biology chemistry.chemical_compound Nucleic acid thermodynamics Nuclear magnetic resonance Nucleic Acid Denaturation chemistry Duplex (building) DNA
Zdroj:	Biochemistry. 52:1354-1363
ISSN:	1520-4995 0006-2960
Popis:	The spiroiminodihydantoins (Sp) are highly mutagenic oxidation products of guanine and 8-oxo-7,8-dihydroguanine in DNA. The Sp lesions have recently been detected in the liver and colon of mice infected with Helicobacter hepaticus that induces inflammation and the development of liver and colon cancers in murine model systems [Mangerich, A., et al. (2012) Proc. Natl. Acad. Sci. U.S.A. 109, E1820–E1829]. The impact of Sp lesions on the thermodynamic characteristics and the effects of the diastereomeric Sp-R and Sp-S lesions on the conformational features of double-stranded 11-mer oligonucleotide duplexes have been studied by a combination of microcalorimetric methods, analysis of DNA melting curves, and two-dimensional nuclear magnetic resonance methods. The nonplanar, propeller-like shapes of the Sp residues strongly diminish the extent of local base stacking interactions that destabilize the DNA duplexes characterized by unfavorable enthalpy contributions. Relative to that of an unmodified duplex, the th...
Databáze:	OpenAIRE
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