Cyclic peptides typically have much higher stability and improved biopharmaceutical properties over their linear
counterparts. Our work focuses on the discovery of naturally occurring disulfide-rich cyclic peptides and their applications
in drug design. These peptides provide a design basis for re-engineering natural acyclic peptides to improve their
biopharmaceutical properties by chemically linking their termini. Here we describe examples of the discovery of the cyclotide
family of peptides, their chemical re-engineering to introduce desired pharmaceutical activities, studies of their biopharmaceutical
properties and applications of cyclization technologies to naturally occurring toxins, including conotoxins
and scorpion toxins. In the case of the conotoxin Vc1.1, we produced an orally active peptide with potential for the treatment
of neuropathic pain by cyclising the native peptide. In the case of the scorpion toxin chlorotoxin, a cyclised derivative
had improved biopharmaceutical properties as a tumour imaging agent over the naturally occurring linear chlorotoxin.
Ongoing chemical and structural studies of these classes of disulfide-rich peptides promise to increase their value for use
in dissecting biological processes in plants and mammals while also providing leads to new classes of biopharmaceuticals.
Keywords: Chlorotoxin, conotoxin, cyclic peptides, cyclotide, kalata B1, biopharmaceutical properties, cyclic peptides, drug design, acyclic peptides, cyclization technologies, scorpion toxins, neuropathic pain, scorpion toxin chlorotoxin, native peptide, neurotransmitters
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