In situ electrochemical and AFM study of thalidomide–DNA interaction |
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Authors: | SCB Oliveira AM Chiorcea-Paquim SM Ribeiro ATP Melo M Vivan AM Oliveira-Brett |
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Institution: | aDepartamento de Química, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal;bDepartamento de Bioquímica, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal;cHospital da Universidade de Coimbra, 3000 Coimbra, Portugal |
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Abstract: | The interaction of thalidomide (TD) with double-stranded DNA (dsDNA) was studied using atomic force microscopy (AFM) at highly oriented pyrolytic graphite (HOPG), differential pulse voltammetry (DPV) at glassy carbon electrodes (GCE), UV–Vis and electrophoresis. After incubation of dsDNA with different concentrations of TD, the AFM images show the formation of thin and incomplete TD–DNA network films with a number of embedded molecular aggregates and regions of uncovered HOPG. Both the TD–dsDNA aggregates and network thickness directly depended on the TD concentration and incubation time. The voltammetric data also showed that the modifications caused by TD to the DNA double helical structure are time-dependent. In agreement with AFM, DPV, UV–Vis and electrophoresis results, a model is proposed for the TD–DNA interaction, considering that TD intercalates into the dsDNA, causing defects in the dsDNA secondary structure and DNA double helix unwinding. Moreover, both AFM and DPV show that condensation is caused to DNA by TD and occurs until 24 h of incubation, as well as DNA oxidative damage, detected electrochemically by the appearance of the 8-oxoGua and/or 2,8 oxoAde oxidation peak. |
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Keywords: | Thalidomide Thalidomide– DNA interaction DNA-damage Voltammetry AFM |
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