Recent progress towards pharmaceutical applications of disulfide-rich cyclic peptides

Schroeder, Christina I., Swedberg, Joakim E. and Craik, David J. (2013) Recent progress towards pharmaceutical applications of disulfide-rich cyclic peptides. Current Protein and Peptide Science, 14 6: 532-552. doi:10.2174/13892037113149990069

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Author Schroeder, Christina I.
Swedberg, Joakim E.
Craik, David J.
Title Recent progress towards pharmaceutical applications of disulfide-rich cyclic peptides
Journal name Current Protein and Peptide Science   Check publisher's open access policy
ISSN 1389-2037
1875-5550
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.2174/13892037113149990069
Open Access Status Not yet assessed
Volume 14
Issue 6
Start page 532
End page 552
Total pages 21
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Language eng
Abstract Cyclotides and conotoxins are two classes of disulfide-rich peptides that occur in plants and animals respectively and are the major focus of study in our laboratory. In the last three years there has been significant progress in studies of these two classes of compounds and in this article we provide an overview of the findings from our laboratory in this period. Highlights include the discovery of cyclotides in the Fabaceae and Solanaceae plant families, members of which are widely used in human nutrition, and the discovery of new classes of cyclotide precursors. These discoveries confirm the widespread distribution of cyclotides in the plant kingdom and the diversity of precursor proteins involved in their biosynthesis. Other studies have delineated the mode of action of naturally occurring cyclotides and have demonstrated the versatility of synthetic cyclotides as stable protein engineering frameworks, with applications in drug design. Conotoxins continue to be a rich source of inspiration for drug design programs, and we summarize here a range of recent studies from our laboratory focusing on the development of novel synthetic strategies and the delineation of structure-activity relationships. A major highlight was the development of an orally active cyclized conotoxin derivative that is highly efficacious in a rat model of neuropathic pain. Overall the studies described herein provide much encouragement for continuing efforts to develop peptides as drugs.
Formatted abstract
Cyclotides and conotoxins are two classes of disulfide-rich peptides that occur in plants and animals respectively and are the major focus of study in our laboratory. In the last three years there has been significant progress in studies of these two classes of compounds and in this article we provide an overview of the findings from our laboratory in this period. Highlights include the discovery of cyclotides in the Fabaceae and Solanaceae plant families, members of which are widely used in human nutrition, and the discovery of new classes of cyclotide precursors. These discoveries confirm the widespread distribution of cyclotides in the plant kingdom and the diversity of precursor proteins involved in their biosynthesis. Other studies have delineated the mode of action of naturally occurring cyclotides and have demonstrated the versatility of synthetic cyclotides as stable protein engineering frameworks, with applications in drug design. Conotoxins continue to be a rich source of inspiration for drug design programs, and we summarize here a range of recent studies from our laboratory focusing on the development of novel synthetic strategies and the delineation of structureactivity relationships. A major highlight was the development of an orally active cyclized conotoxin derivative that is highly efficacious in a rat model of neuropathic pain. Overall the studies described herein provide much encouragement for continuing efforts to develop peptides as drugs.
Keyword Conotoxins
Cyclic peptides
Cyclization
Cyclotides
Drug design
Pain
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP1093115
ID631457
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 21 times in Scopus Article | Citations
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Created: Tue, 17 Sep 2013, 23:45:48 EST by Susan Allen on behalf of Institute for Molecular Bioscience