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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Role of 4-Thiazolidinone Scaffold in Targeting Variable Biomarkers and Pathways Involving Cancer
Anti-Cancer Agents in Medicinal Chemistry Superparamagnetic Magnetite (Fe3O4) Nanoparticles for Bio-Applications
Recent Patents on Materials Science The Ubiquitin-Proteasome System (UPS) and the Mechanism of Action of Bortezomib
Current Pharmaceutical Design Gene Expression Analysis Approach to Establish Possible Links Between Parkinson's Disease, Cancer and Cardiovascular Diseases
CNS & Neurological Disorders - Drug Targets Recent Patents of Gene Sequences Relative to the Phosphatidylinositol 3-kinase / Akt Pathway and their Relevance to Drug Discovery
Recent Patents on DNA & Gene Sequences Cdc25A Protein Phosphatase: A Therapeutic Target for Liver Cancer Therapies
Anti-Cancer Agents in Medicinal Chemistry Molecular Probing and Imaging of Histone Deacetylase Inhibitors in Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Polyphenols and Neuroprotection against Ischemia and Neurodegeneration
Mini-Reviews in Medicinal Chemistry Application of Metabolomics in Drug Discovery, Development and Theranostics
Current Metabolomics Anti-inflammatory and Immune Therapy for Alzheimers Disease: Current Status and Future Directions
Current Neuropharmacology Emerging Facts on Chronic Consumption of Aspartame as Food Additive
Current Nutrition & Food Science Antioxidant, Anti-Inflammatory and Cytotoxic Properties of <i>Centaurea africana</i> Lamk var. [Bonnet] M
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Synthesis and In Vitro Evaluation of Novel 1,2,3,4-Tetrahydroisoquinoline Derivatives as Potent Antiglioma Agents
Anti-Cancer Agents in Medicinal Chemistry The Role of CD40 Expression in Dendritic Cells in Cancer Biology; A Systematic Review
Current Cancer Drug Targets The Role of Glioma Microenvironment in Immune Modulation: Potential Targets for Intervention
Letters in Drug Design & Discovery A Review on Chitosan in Drug Delivery for Treatment of Neurological and Psychiatric Disorders
Current Pharmaceutical Biotechnology Transforming Growth Factor-β: A Molecular Target for the Future Therapy of Glioblastoma
Current Pharmaceutical Design The Pivotal Role of Multimodality Reporter Sensors in Drug Discovery: From Cell based Assays to Real Time Molecular Imaging
Current Pharmaceutical Biotechnology Role of Translocator Protein in Renal Ischemia Reperfusion, Renal Preservation and Acute Kidney Injury
Current Molecular Medicine The mTOR Signaling Network: Insights from Its Role During Embryonic Development
Current Medicinal Chemistry