Formation mechanism of glyoxal-DNA adduct, a DNA cross-link precursor

Show simple item record Vilanova Canet, Bartolomé Fernández Payeras, David Casasnovas Perera, Rodrigo Pomar, A.M. Alvarez-Idaboy, J.R. Hernández-Haro, Noemí Grand, A. Adrover Estelrich, Miguel Donoso Pardo, Josefa Laurentina Frau Munar, Juan Muñoz Izquierdo, Francisco Ortega Castro, Joaquín 2018-10-15T10:56:47Z
dc.description.abstract [eng] DNA nucleobases suffer non-enzymatic glycation, generating nucleobase adducts that can play an important role in vivo. In this work, we have carried out a completed experimental and theoretical kinetic study of the mechanisms of formation of glyoxal-guanine adducts in a wide pH region in order to understand the molecular basis of the glycation process. On the other hand, molecular dynamics simulations have been performed to elucidate how open or cyclic glyoxal-guanine adducts might cause structural changes in an oligonucleotide model. A thermodynamic study with other glycating agents (methylglyoxal, acrolein, crotonaldehyde, 4-hydroxynonenal and 3-deoxyglucosone) has been done and we show that, at neutral pH, the cyclic adducts were more stable than the open ones; whereas at basic pH, the open adduct structures of 3-deoxyglucosone, methylglyoxal, and glyoxal were most stable than the cyclic ones. This fact is related to the propensity of these adducts to cross-link DNA. Our new insights contribute toward a better understanding of the link between glycation and DNA cross-link.
dc.format application/pdf
dc.relation.isformatof Versió postprint del document publicat a:
dc.relation.ispartof International Journal of Biological Macromolecules, 2017, vol. 98, p. 664-675
dc.subject.classification 54 - Química
dc.subject.other 54 - Chemistry. Crystallography. Mineralogy
dc.title Formation mechanism of glyoxal-DNA adduct, a DNA cross-link precursor
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion 2018-10-15T10:56:47Z info:eu-repo/date/embargoEnd/2075-01-01
dc.embargo 2075-01-01
dc.subject.keywords Non-enzymatic glycation
dc.subject.keywords Molecular Dynamics
dc.subject.keywords DFT calculations
dc.subject.keywords human DNA
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess

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