SAGE-Hindawi Access to Research Journal of Nucleic Acids Volume 2010, Article ID 489060, 10 pages doi:10.4061/2010/489060 Research Article Synthesis and G-Quadruplex-Binding Properties of Defined Acridine Oligomers Rub´ en Ferreira, 1 Anna Avi˜ n´ o, 1 Ricardo P´ erez-Tom´ as, 2 Raimundo Gargallo, 3 and Ramon Eritja 1 1 Institute for Research in Biomedicine, IQAC-CSIC, CIBER-BBN Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Edifici Helix, Baldiri Reixac 15, 08028 Barcelona, Spain 2 Cancer Cell Biology Research Group, Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona Campus Bellvitge, Feixa Llarga, L’Hospitalet de Llobregat, 08907 Barcelona, Spain 3 Department of Analytical Chemistry, University of Barcelona, Diagonal 647, 08028 Barcelona, Spain Correspondence should be addressed to Ramon Eritja, recgma@cid.csic.es Received 14 January 2010; Revised 22 March 2010; Accepted 13 April 2010 Academic Editor: Daniela Montesarchio Copyright © 2010 Rub´ en Ferreira et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The synthesis of oligomers containing two or three acridine units linked through 2-aminoethylglycine using solid-phase methodology is described. Subsequent studies on cell viability showed that these compounds are not cytotoxic. Binding to several DNA structures was studied by competitive dialysis, which showed a clear affinity for DNA sequences that form G-quadruplexes and parallel triplexes. The fluorescence spectra of acridine oligomers were affected strongly upon binding to DNA. These spectral changes were used to calculate the binding constants (K). Log K were found to be in the order of 4–6. 1. Introduction Small organic molecules with specific interactions with DNA have become antitumor, antiviral, and antibiotic drugs [1, 2]. Duplex DNA-binding drugs interact in two main ways, through groove binding and through intercalation. Medic- inal chemistry has made a considerable effort in searching for and testing of a large number of drugs with increased selectivity to a range of DNA sequences or structures. More recently, some of this interest has moved to the search of new ligands for G-quadruplexes [3]. This structure motif is formed by the planar association of four guanines in a cyclic Hoogsteen hydrogen bonding tetrad. Guanine-rich sequences form G-quadruplex structures and have been found in telomeres [4] and in transcriptional regulatory regions of critical oncogenes such as c-myc and c-kit [5, 6]. Ligands that selectively bind and stabilize these structures have become anticancer drugs of interest [7]. The G-quadruplex stabilization occurs in most cases by π -π stacking and electrostatic interaction. G-quadruplex ligands are normally planar aromatic molecules that are prone to stacking with G-tetrads. Some of them are also positively charged or have hydrophilic groups to favor electrostatic interaction [8]. Although there is a long way to go in the develop- ment of potent drugs that target G-quadruplexes, some promising lead compounds have been achieved [9]. Several ligand structures have been studied, such as anthraquinones, cationic porphyrins, perylene derivatives, and a large num- ber of compounds [9]. Among the acridine compounds, 3,6,9-trisubstituted acridines have inhibitory activity in the nanomolar range and they have entered preclinical studies [8, 10, 11]. In previous studies we described the preparation of sequence specific oligomers of DNA-intercalating drugs using protocols based on solid-phase synthesis in an attempt to facilitate the preparation of compounds with improved DNA-binding selectivity [12, 13]. It has been proposed that bis- and tris-intercalating drugs show promising activity and selectivity [14, 15]. Here we described solid-phase synthesis protocols for the preparation of several acridine oligomers linked through 2-aminoethylglycine units as well as their DNA-binding properties. Although the acridine derivatives described in this study are not cytotoxic, they show a clear