Conformational dynamics in peptide toxins: Implications for receptor interactions and molecular design
Karoline Sanchesa,b,1, Dorothy C.C. Waia,1, Raymond S. Nortona,b
aMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia
bARC Centre for Fragment-Based Design, Monash University, Parkville, Victoria, 3052, Australia
1These authors contributed equally
Peptide toxins are often potent and selective blockers of ion channels and are therefore of significant interest to the pharmaceutical and biotech industries. For example, an analogue of the sea anemone peptide ShK, which targets the voltage-gated potassium channel Kv1.3, is currently in clinical trials for the treatment of autoimmune disorders. Studying the structure-function relationship and the dynamics of these peptides is pivotal to understanding their binding to receptors, as well as to designing new drugs. In this article, we highlight the important contribution of NMR to characterising peptide toxin dynamics. It is shown that even disulphide-rich peptides display dynamics in various timescales, the characterisation of which through NMR is crucial for understanding their receptor interactions.