title: In situ evaluation of gemcitabine-DNA interaction using a DNA-electrochemical biosensor.
abstract: The electrochemical behaviour of the cytosine nucleoside analogue and anti-cancer drug gemcitabine (GEM) was investigated at glassy carbon electrode, using cyclic, differential pulse and square wave voltammetry, in different pH supporting electrolytes, and no electrochemical redox process was observed. The evaluation of the interaction between GEM and DNA in incubated solutions and using the DNA-electrochemical biosensor was studied. The DNA structural modifications and damage were electrochemically detected following the changes in the oxidation peaks of guanosine and adenosine residues and the occurrence of the free guanine residues electrochemical signal. The DNA-GEM interaction mechanism occurred in two sequential steps. The initial process was independent of the DNA sequence and led to the condensation/aggregation of the DNA strands, producing rigid structures, which favoured a second step, in which the guanine hydrogen atoms, participating in the C-G base pair, interacted with the GEM ribose moiety fluorine atoms.
authors.affiliation: Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal; Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, Brazil.
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Buoro
authors.affiliation: Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Ilanna C
authors.initials: IC
authors.lastname: Lopes
authors.affiliation: Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Diculescu
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, Brazil.
authors.forename: Silvia H P
authors.initials: SH
authors.lastname: Serrano
authors.affiliation: Serviços Farmacêuticos, Centro Hospitalar e Universitário de Coimbra (CHUC), 3000-075 Coimbra, Portugal.
authors.forename: Liseta
authors.initials: L
authors.lastname: Lemos
authors.affiliation: Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal. Electronic address: brett@ci.uc.pt.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Oliveira-Brett
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015374:Biosensing Techniques / Q000379:methods; D004247:DNA / Q000737:chemistry*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D055664:Electrochemical Techniques / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D010084:Oxidation-Reduction; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D004247:DNA; D000093542:Gemcitabine
keywords: DNA; Electrochemical DNA-biosensor; Gemcitabine; Guanine; Interaction mechanism