Nuclear magnetic resonance (NMR) spectroscopy is in principle an ideal tool for chemical, structural and functional characterisation of peptides.1 However, peptides also pose challenges, including poor sensitivity in measurement of distance restraints, difficulties in recombinant expression for isotope labeling and ambiguities introduced by high levels of local flexibility. Many of these difficulties can, however, be overcome by recent progress in NMR technology and methodology as well as the application of advanced biochemical tools.
Here I will focus on our work on structural and functional characterisation of disulfide rich peptides, including hormones and venom peptides.2 I will discuss methods we have developed that (i) provide unprecedented high-resolution structural details of peptides in solution (ii) enable production and studies of tandem repeats of disulfide rich peptides and (iii) are applied to study the interaction of peptides with lipid membranes and membrane bound receptors.
These advances will be presented in the context of our ongoing efforts in drug screening and rational drug design, with a focus on membrane bound receptors such as voltage-gated ion channels.