The development of molecules that selectively bind to nucleic acids has provided many details about DNA and RNA recognition. The range of such substances, such as metal complexes, peptides, oligonucleotides and a wide array of synthetic organic compounds, is as manifold as the functions of nucleic acids. Nucleic acid recognition sequences are often found in the major or minor groove of a double strand, while other typical interactions include intercalation between base pairs or the formation of triple or quadruple helices. One example of a binding mode that has recently been proposed is end stacking on such complex structures as the telomere tetraplex. In this comprehensive book, internationally recognized experts describe in detail the important aspects of nucleic acid binding, and in so doing present impressive approaches to drug design. Since typical substances may be created naturally or synthetically, emphasis is placed on natural products, chemical synthesis, the use of combinatorial libraries, and structural characterization. The whole is rounded off by contributions on molecular modeling, as well as investigations into the way in which any given drug interacts with its nucleic acid recognition site.

Discover a new paradigm in drug discovery that greatly expands the space of addressable drug targets and potential novel drugs Existing paradigms for drug discovery have focused largely on enzymes and other proteins as drug targets. In recent years, however, different varieties of ribonucleic acids have emerged as a viable focus for target-based drug discovery, with the potential to revolutionize the strategy and approach for this essential step in the drug development process. RNA as a Drug Target: The Next Frontier for Medicinal Chemistry offers a practice-oriented introduction to developing drug-like small molecules that selectively modulate both coding and non-coding RNAs. Beginning with a description and characterization of existing druggable RNAs, the book discusses how to approach different RNA targets for drug discovery. The result is a crucial resource for targeting RNAs and creating the next generation of life-saving pharmaceuticals. RNA as a Drug Target readers will also find: A complete “toolbox” for working with RNA, from structure determination to screening and lead generation techniques A wide range of addressable targets and mechanisms, including splicing modulation, riboswitches, targeted degradation, and more Authoritative discussion of the potential of RNA-targeted small molecule therapeutics for drugging the epitranscriptome RNA as a Drug Target provides an expert introduction to a new frontier in pharmaceutical research for medicinal chemists, biochemists, molecular biologists, and members of the pharmaceutical industry.

Deoxyribonucleic acid (DNA) is a fundamental component in all living organisms found in Nature. Although both the double-helix structure of this biomolecule and the fact that it stores all the genetic information required by the organism to survive are well understood there are still aspects related to this molecule which are not as clear. Particularly the interactions underpinning the formation of complexes between other molecules, such as proteins, and DNA remain unclear. One of these is the process underlying the formation of small molecule-DNA complexes. Such complexes are known to form via interactions between these small molecules and the DNA minor groove, it has proven to be complicated to develop a set of rational rules for the synthesis of binders to target particular DNA sequences. Such rules are complicated by the complex molecular environment found within the DNA minor groove as well as the role of the spine of hydration found within this groove. Another aspect of the behaviour of DNA which has attracted a lot of attention is related to the mechanism underlying the melting of short DNA sequence. It is important to gain a better understanding of these mechanisms as this process is thought to be important in DNA transcription, replication and repair as well as being important for the application and development of DNA scaffolds. Additionally, it is thought that understanding the impact of binding on this transition could be used to gain further insights into the interactions underpinning these complexes.