G-quadruplex ligands: A selective approach to telomeres length regulation, both directly and through telomerase inhibition

G-quadruplex represents a group of unusual DNA secondary structures, based on Hoogsteen G-G pairing hydrophobic planar rings of four guanines. Many studies have reported that G-quadruplex structures appear to be involved in many important biological processes, such as DNA replication, gene expression and recombination, as well as cell transformation. The G-quadruplex has been shown to be specifically important in the structure of G-rich single-strand DNA at the end of telomeres. The presence of these structures in vivo has been demonstrated in a number of biological systems, ranging form ciliates to humans. For these reasons, in the last few years, the research of specific G-quadruplex ligands as potential drugs has gained major attention, in particular as telomeres targeting agents and telomerase inhibitors and thus potential anticancer drugs. Many eminent scientists have been working in this exciting field, as demonstrated by the success of the First International Meeting on Quadruplex DNA, held in Louisville (KY, USA) in April 2007§. The specificity of the interactions between the studied ligands and different DNA structures (both duplex and quadruplex) is surely a main topic in this area, since it determines the different biological effects of these compounds. Several approaches have been used to explore this subject, and they will be briefly summarized in this chapter. Nevertheless, particular attention should be paid when comparing biological data from different labs on telomerase inhibition by these compounds. In fact, these data, which are very important from a pharmaceutical and medicinal chemistry point of view, are affected by many factors, such as the type of cells used to extract telomerase, the presence of proteins other than telomerase in the cell extract, the amount of cell extract and DNA substrates used, as well as other features that have not been fully standardized yet. © 2011 by Nova Science Publishers, Inc. All rights reserved.