Bioactive cystine knot proteins

The cystine knot is a structural motif that confers exceptional stability on proteins. Here we provide an update on the topology of the cystine knot and the combinatorial diversity of proteins that contain it. We describe recent chemical biology studies that have utilised this structural motif for the development of potential therapeutic or diagnostic agents. The cystine knot appears to have evolved in fungi, plants and animals as a stable and adaptable framework for the display of a wide variety of bioactive peptide sequences, but is amenable to chemical or recombinant synthesis and thus has a wide range of applications in chemistry, biology and medicine.