Abstract
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
Current Topics in Medicinal Chemistry
Title:Discovery and Applications of Disulfide-Rich Cyclic Peptides
Volume: 12 Issue: 14
Author(s): Masa Cemazar, Soohyun Kwon, Tunjung Mahatmanto, Anjaneya S. Ravipati and David J. Craik
Affiliation:
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
Abstract: 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.
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Cite this article as:
Cemazar Masa, Kwon Soohyun, Mahatmanto Tunjung, S. Ravipati Anjaneya and J. Craik David, Discovery and Applications of Disulfide-Rich Cyclic Peptides, Current Topics in Medicinal Chemistry 2012; 12 (14) . https://dx.doi.org/10.2174/156802612802652484
DOI https://dx.doi.org/10.2174/156802612802652484 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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