DNA Major Groove Binders: Triple Helix-Forming Oligonucleotides, Triple Helix-Specific DNA Ligands and Cleaving Agents

Abstract

Nucleic acids are polymorphic macromolecules that can adopt a variety of single-, double- and multi-stranded conformations, which in turn may provide important signals for regulating gene expression, and for maintaining genome integrity and stability. The design of tailor-made molecules that recognize specific sequences in the DNA double helix would provide interesting tools to interfere with DNA information processing and to target genome modifications. The ability to specifically manipulate genetic information processing genome-wide offers a variety of applications in experimental biology as well as gene-based biotechnology and therapeutics. It presents an important challenge in biological and biomedical sciences. This chapter will cover the topic of sequence-specific ligands that bind within and recognize the major groove of the DNA double helix. In particular, it will focus on the development of triple helix-forming oligonucleotides as highly sequence-specific DNA major groove binders, the related triple helix structures, examples of triple helix-specific ligands and DNA cleaving agents, as well as their biological relevance, during the last 10–15 years.