Polycyclic Peptide Therapeutics
- 25 January 2013
- journal article
- review article
- Published by Wiley in ChemMedChem
- Vol. 8 (3), 377-384
- https://doi.org/10.1002/cmdc.201200513
Abstract
Owing to their excellent binding properties, high stability, and low off‐target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish‐hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases.Keywords
This publication has 58 references indexed in Scilit:
- Bicyclization and Tethering to Albumin Yields Long-Acting Peptide AntagonistsJournal of Medicinal Chemistry, 2012
- Structurally Diverse Cyclisation Linkers Impose Different Backbone Conformations in Bicyclic PeptidesChemBioChem, 2012
- HDAC inhibitors in cancer biology: emerging mechanisms and clinical applicationsImmunology & Cell Biology, 2011
- Structural Basis of the Antiproliferative Activity of Largazole, a Depsipeptide Inhibitor of the Histone DeacetylasesJournal of the American Chemical Society, 2011
- Small-molecule discovery from DNA-encoded chemical librariesChemical Society Reviews, 2011
- Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphomaThe Journal of Antibiotics, 2011
- Engineered Cystine Knot Miniproteins as Potent Inhibitors of Human Mast Cell Tryptase βJournal of Molecular Biology, 2010
- A Combinatorial Approach for the Design of Complementarity-determining Region-derived Peptidomimetics with in Vitro Anti-tumoral ActivityOnline Journal of Public Health Informatics, 2009
- Biological diversity and therapeutic potential of natural and engineered cystine knot miniproteinsCurrent Opinion in Pharmacology, 2009
- Engineered Cystine-Knot Peptides that Bind αvβ3 Integrin with Antibody-Like AffinitiesJournal of Molecular Biology, 2009