NMR and protein structure in drug design: application to cyclotides and conotoxins

Daly, Norelle L., Rosengren, K. Johan, Henriques, Sónia Troeira, and Craik, David J. (2011) NMR and protein structure in drug design: application to cyclotides and conotoxins. European Biophysics Journal, 40 (4). pp. 359-370.

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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.

Item ID: 27037
Item Type: Article (Research - C1)
ISSN: 1432-1017
Keywords: cyclic peptide cyclotide, conotoxin, Kalata B1, structure–activity relationships
Funders: Australian Research Council (ARC), National Health and Medical Research Council (NHMRC)
Date Deposited: 23 May 2013 02:02
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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