CHAPTER 15: Cyclic Peptides – A Look to the Future
Published:14 Dec 2017
C. N. Alexandru-Crivac, L. Dalponte, W. E. Houssen, M. Idress, M. Jaspars, K. A. Rickaby, and L. Trembleau, in Cyclic Peptides: From Bioorganic Synthesis to Applications, ed. J. Koehnke, J. Naismith, and W. A. van der Donk, The Royal Society of Chemistry, 2017, pp. 340-373.
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This chapter sums up the different approaches to harness the promising therapeutic potential of cyclic peptides in drug discovery and proposes a number of areas which need improvement in order to make cyclic peptides live up to their full potential as drug candidates. It is clear that improved methods to rapidly and efficiently synthesize cyclic peptides and modify them are essential to explore this region of chemical space. A better understanding of what governs the physicochemical characteristics of this compound class is essential to allow the better prediction of the properties of designed cyclic peptides. With this goes the ability to accurately and reliably predict the solution and binding conformations of cyclic peptides, as well as theoretical approaches for determining which peptides are likely to cyclize easily, and which are not. How such compounds bind to their target proteins is just beginning to be understood and improvements are necessary to allow the design of cyclic peptides that bind specifically to extended binding sites. Finally, the ability to utilize biosynthetic machineries from diverse pathways to create hybrid molecules with desirable characteristics is proposed as a major target for future investigation.