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.
Keywords: Conotoxins, cyclic peptides, cyclization, cyclotides, drug design, pain.
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Published on: 31 August, 2013
Page: [532 - 552]