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Title: Self-association of isoguanine nucleobases and molecular recognition of alkaline ions: Tetrad versus pentad structures
P105
Meyer, M.; Suehnel, J.

m.meyer@revotar-ag.de, jsuehnel@imb-jena.de
Revotar Biopharmaceuticals AG, Neuendorfstr. 24b, D-16761 Hennigsdorf / Germany and Institute of Molecular Biotechnology, Jena Centre for Bioinformatics, Beutenbergstr. 11, D-07745 Jena / Germany

Multi-stranded nucleic acid structures contain as basic building blocks base polyads instead of the base pairs found in conventional double helices. Such unusual DNA or RNA structures have recently attracted much interest since they are involved in many important biological functions; for a review see [1]. Examples include gene targeting via DNA triplexes and tetraplex structures occurring in telomeres at the ends of eukaryotic linear chromosomes, in structures formed from triplet repeat expansion disease sequences, from control regions of oncogenes, and from centromere sequences. Finally, RNA tetraplex motifs have been identified in mRNAs that are recognized by the fragile X syndrome protein. Due to this biological relevance nucleic acid tetraplexes have also been considered as an important drug target. Finally, because the formation of these structures requires the presence of metal ions structures of this type also play a role for cation recognition in supramolecular chemistry.

Recently, it has been reported that isoguanine oligonucleotides assemble to cyclic pentad structures in the presence of large Cs+ ions, whereas tetrad structures are formed with the smaller Na+ ions [2-4].

We have performed B3LYP hybrid density functional studies of complexes between alkaline ions and cyclic isoguanine tetrads and pentads and found a theoretical rationale for the ion-dependent optimal number of nucleobase ligands. Except for Li+ all tetrad cation complexes are strongly non-planar, whereas all pentad complexes, except for Cs+, are planar. For all investigated model systems the polyad cation interaction is the dominant contribution to the interaction energy. In tetrads the hydrogen bond pattern changes when passing from the free to the metal-ion containing complexes. A comparison of the interaction energies per base indicates that the formation of tetrad ion complexes is generally favoured for smaller ions. However, for large ions the difference of the interaction energy per base in tetrads and pentads vanishes. Further, the interaction energy between the tetrad and alkaline ions exceeds the one between the ion and the pentad. For alkaline ions with large ions the opposite relation holds. This explains the experimental observation that small ions induce tetraplex formation, whereas in the presence of large ions pentaplex structures are preferred.
[1] J. Sühnel, Biopolymers 2001-2002, 61, 32-51.
[2] F. Seela, C. Wei, A. Melenewki, Nucl. Acids Res. 1996, 24, 4940-4945.
[3] F. Seela, R. Kroschel, Bioconj. Chem. 2001, 12,1043-1050.
[4] J. C. Chaput, C. Switzer, Proc. Natl. Acad. Sci. 1999, 96, 10614-10619.