1 Bioactive Macrocyclic Peptides and Peptide Mimics

The number of both naturally occurring and synthesized biologically active cyclic peptides, modified peptides, and peptide mimics is rapidly increasing. So far, many of these sometimes biologically very potent peptides have unfortunately unknown molecular targets or mechanisms of action. This certainly opens up very interesting and challenging research areas with respect to uncovering these targets and/or molecular mechanisms of biological activity, which – depending on the biological action – can be very promising, for example, for the development of new drugs. However, merely a review of most biologically active cyclic peptides – if this were possible at all – is not the aim of this chapter. Instead, we wish to focus on selected bioactive macrocyclic peptide systems with known molecular peptide or protein targets as well as details about their molecular interaction mechanism. Where possible, we would like to discuss the contribution of the cyclic nature of the peptides to the molecular mechanism of interaction and the ensuing biological activity. We will therefore not include cyclic peptides and mimics merely interacting with membrane lipids or cyclic peptides interacting with DNA or RNA. Each of these topics deserves a review on its own, especially in light of the increasing interest in membrane proteins and transcription activators/regulators. The selection of cyclic peptides interacting with known molecular targets in this chapter is largely determined by their relevance in relation to possible treatments of diseases. In this respect, probably vancomycin and cyclosporin are the most wellknown cyclic peptides containing modified amino acids, which have had a profound influence on the treatment of life-threatening diseases. The vancomycin-related antibiotics [1] are outstanding examples of cyclic peptide systems containing multiple knotted side chains by which almost absolute control over the shape of the molecule is achieved, leading to efficient binding of crucial fragments of the cell-wall precursor of disease-causing bacteria. j1