title: NMR and protein structure in drug design: application to cyclotides and conotoxins.
abstract: Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique for determining the structures, dynamics and interactions of molecules, and the derived information can be useful in drug design applications. This article gives a brief overview of the role of NMR in drug design and illustrates this role with examples studied in our laboratory in recent years on disulfide-rich peptides, including cyclotides and conotoxins. Cyclotides are head-to-tail cyclized proteins from plants that are exceptionally stable and hence make useful templates for the stabilization of bioactive peptide epitopes as well as potential leads for anti-HIV drugs. Natural cyclotides target cell membranes, so understanding cyclotide-membrane interactions is useful in applying cyclotides in drug design applications. NMR studies of these interactions are described in this article. Conotoxins are disulfide-rich peptides, from the venoms of marine cone snails, which are of pharmaceutical interest because they potently interact with a range of ion channels, transporters and other receptor sites implicated in disease states. Chemically re-engineering conotoxins to give them a cyclic backbone has been used to engender them with improved biopharmaceutical properties, such as are observed in cyclotides.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Norelle L
authors.initials: NL
authors.lastname: Daly
authors.forename: K Johan
authors.initials: KJ
authors.lastname: Rosengren
authors.forename: Sónia Troeira
authors.initials: ST
authors.lastname: Henriques
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
mesh_terms: D020916:Conotoxins / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D047169:Cyclotides / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D020916:Conotoxins; D047169:Cyclotides; C091930:kalata B1