Chapter 13:Synthetic Peptides for DNA Recognition Inspired by Transcription Factors

Transcription Factors (TFs) are key players in the conversion of the information held in mRNA into a ’language’ that the body can understand. This they achieve by specifically recognising and binding to short regulatory DNA sequences which control the gene. These interactions between DNA and proteins are extremely specific and of very high affinity. Consequently, much effort has been devoted to elucidating TF structures and their modes of binding to DNA. It is therefore not surprising that TFs have been the main role models for the design and synthesis of DNA-binding peptides. The current chapter, after giving an overview of known TF structures, describes the different peptide-based DNA binding systems that have been conceived and studied, ranging from replacement of the TF dimerization domain by non-peptide scaffolds, through the connection of major-groove-recognising entities to minor-groove binders, to the further miniaturisation of the systems towards monomeric peptide sequences still capable of binding to nucleic acid duplexes. Thanks to these miniaturisation efforts, the systems have finally reached a stage where therapeutic applications can be envisaged.