title: Formation mechanism of glyoxal-DNA adduct, a DNA cross-link precursor.
abstract: DNA nucleobases undergo non-enzymatic glycation to nucleobase adducts which can play important roles in vivo. In this work, we conducted a comprehensive experimental and theoretical kinetic study of the mechanisms of formation of glyoxal-guanine adducts over a wide pH range in order to elucidate the molecular basis for the glycation process. Also, we performed molecular dynamics simulations to investigate how open or cyclic glyoxal-guanine adducts can cause structural changes in an oligonucleotide model. A thermodynamic study of other glycating agents including methylglyoxal, acrolein, crotonaldehyde, 4-hydroxynonenal and 3-deoxyglucosone revealed that, at neutral pH, cyclic adducts were more stable than open adducts; at basic pH, however, the open adducts of 3-deoxyglucosone, methylglyoxal and glyoxal were more stable than their cyclic counterparts. This result can be ascribed to the ability of the adducts to cross-link DNA. The new insights may contribute to improve our understanding of the connection between glycation and DNA cross-linking.
authors.affiliation: Department de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca, Spain. Electronic address: bartomeu.vilanova@uib.es.
authors.forename: B
authors.initials: B
authors.lastname: Vilanova
authors.affiliation: Department de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Fernández
authors.affiliation: Department de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Casasnovas
authors.affiliation: Department de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca, Spain.
authors.forename: A M
authors.initials: AM
authors.lastname: Pomar
authors.affiliation: Facultad de Química, Departamento de Física y Química Teórica, Universidad Nacional Autónoma de México, México D.F. 04510, Mexico.
authors.forename: J R
authors.initials: JR
authors.lastname: Alvarez-Idaboy
authors.affiliation: CEA, INAC-SyMMES, F-38000 Grenoble, France.
authors.forename: N
authors.initials: N
authors.lastname: Hernández-Haro
authors.affiliation: Univ. Greboble Alpes, INAC-SCIB, F-38000 Grenoble, France; CEA, INAC-SyMMES, F-38000 Grenoble, France; Universidad Autónoma de Chile, Carlos Antúnez 1920, 7500566, Providencia, Santiago de, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Grand
authors.affiliation: Department de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Adrover
authors.affiliation: Department de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Donoso
authors.affiliation: Department de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Frau
authors.affiliation: Department de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Muñoz
authors.affiliation: Department de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de Palma (IdISPA), 07010 Palma de Mallorca, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ortega-Castro
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D018736:DNA Adducts / Q000737:chemistry* / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D006031:Glycosylation; D006037:Glyoxal / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D007700:Kinetics
chemical_list: D000447:Aldehydes; D018736:DNA Adducts; D006037:Glyoxal; D006147:Guanine; D004247:DNA