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Realised by ALMS™
developer of the AIDS-HIV Reference project
Abstract No.: TuP-086
Session: Drug Discovery and Development
Presentation date: Tue, Aug 29, 2006
Presentation time: 14:30 – 16:00

Behavior of β-carboline Toward Nucleosides, Nucleobases and Oligonucleotides in Electrospray

Ying Xu1,2, Clotilde Le Vot1, Xiao Chun Dong2, Carlos Afonso1, Francoise Founier1, Ren Wen2, Jean-Claude Tabet1

1 University Pierre and Marie Curie, Paris, France
2 Fudan University, Shanghai, China

Correspondence address: Ying Xu, University Pierre and Marie Curie, Mass spectrometry group, UMR 7613, 4, place Jussieu, Paris, 75252 cedex 05 France.

Keywords: Alkaloids; Complex, Non-Covalent; Nucleobases; Oligonucleotides.

Novel aspect: Study of β-carboline derivativesí affinity and interaction mechanism with oligonucleotides using mass spectrometry.


Thanks for its important biological activity, alkaloid family is very used in therapy treatment. Some alkaloids have been shown to work against cancer, such as β-carboline. In our previous work, non-convalent interaction of two β-carbolines (1, 2) with monodeoxynucleotides were studied with mass spectrometry. With a quasi-planar aromatic structure, it is suggested that 1 and 2 could be used as DNA intercalator,1 which associate with G-C base pair of DNA. The study of deprotonated heterodimerís gas-phase stability showed that 1 and 2 had a most important affinity with dpG, as expected. In this work, the gas phase behavior of β-carbolines towards oligonucleotides was studied. In addition, their non-covalent interactions with deoxynucleosides and nucleobases were also studied.

The gas-phase stabilities of non-covalent complexes were ranked in relative term by their half-wave resonant excitation amplitude in ion trap (V1/2). The stability of deprotonated deoxynucleoside/β-carboline heterodimer was in agreement with relative deoxynucleoside acidity scale for 1 and 2: dG>dT>dC>dA.2 The similar experience was performed with nucleobases, the deprotonated heterodimerís relative stability order was Gua>Thy≈Ade, but the Cyt/β-carboline complex was not observed. Interestingly, this relative stability order differs to the acidity scale of the nucleobase.3 Indeed, Gua is not the most acidic nucleobase but for another time, it presents the most important affinity. These results showed a special interaction between β-carbolines and Gua, which is similar to those, obtained with dN and dpN. It could suggest an electrostatic interaction, which can furthermore confirm that the binding mode of these compounds involve major groove intercalation. Then, the non-covalent complexes of oligonucleotides and β-carbolines were studied by nano electrospray, we obtained once again the similar behavior. So we could suppose that the target of β-carbolines is the G-C pair of the DNA double strand, especially the G part.

1. B. H. Geierstanger, D. E. Wemmer, Annual Rev. Biophys. Biomol. Struct. 24, 463 (1995).
2. A. Delvolve, S. Mezzache, C. Afonso, F. Fournier, S. Bregant, F. Burlina, J.-C. Tabet, Proc. 52th ASMS Conf. (2004).
3. M. T. Rodgers, S. Campbell, E. M. Marzluff, J. L. Beauchamp, Int. J. Mass Spectrom. Ion Processes 137, 121 (1994).