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

Daly, Norelle L., Rosengren, K. Johan, Henriques, Sonia Troeira and Craik, David J. (2011) NMR and protein structure in drug design: Application to cyclotides and conotoxins. European Biophysics Journal, 40 4: 359-370. doi:10.1007/s00249-011-0672-9

Author Daly, Norelle L.
Rosengren, K. Johan
Henriques, Sonia Troeira
Craik, David J.
Title NMR and protein structure in drug design: Application to cyclotides and conotoxins
Journal name European Biophysics Journal   Check publisher's open access policy
ISSN 0175-7571
Publication date 2011-04
Sub-type Article (original research)
DOI 10.1007/s00249-011-0672-9
Volume 40
Issue 4
Start page 359
End page 370
Total pages 12
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2012
Language eng
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.
Keyword Cyclic peptide cyclotide
Kalata B1
Structure–activity relationships
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes From the issue entitled "Special issue: Membrane-active peptides"

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 13 Oct 2011, 16:49:50 EST by Professor David Craik on behalf of School of Biomedical Sciences