Abstract
The long-lasting impetus to design novel modes of macrocyclization, and their implementation into a wide range of bioactive peptides, originates from their contributions to the restriction of conformational space and the stabilization of preferential bioactive conformations that support higher efficacy and binding affinity to cognate macromolecular targets, improved specificity and lowering susceptibility to enzymatic degradation processes. Introducing CuI-catalyzed azide-alkyne cycloaddition (CuAAC), a prototypical click reaction, to the field of peptide sciences as a bio-orthogonal reaction that generates a disubstituted-[1,2,3]triazol-1-yl moiety as a pseudopeptidic bond that is peptidomimetic in nature, paved the way to its widespread application as a new and promising mode of macrocyclization. This review presents the state-of-art of CuAAC-mediated macrocyclization as it applies to an expansive range of bioactive peptides and explores the relationship among the structural diversity of CuAACmediated cyclizations, biological activities and conformations.
Keywords: Copper-catalyzed, pseudopeptides, peptidomimetics, macrocyclization, azide-alkyne, CuAAC-mediated.
Current Topics in Medicinal Chemistry
Title:Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC)-Mediated Macrocyclization of Peptides: Impact on Conformation and Biological Activity
Volume: 18 Issue: 7
Author(s): Chiara Testa, Anna Maria Papini, Michael Chorev*Paolo Rovero*
Affiliation:
- Laboratory for Translational Research, Division of Hematology, Department of Medicine, Brigham and Women`s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115,United States
- French-Italian Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, 50019, Sesto Fiorentino,Italy
Keywords: Copper-catalyzed, pseudopeptides, peptidomimetics, macrocyclization, azide-alkyne, CuAAC-mediated.
Abstract: The long-lasting impetus to design novel modes of macrocyclization, and their implementation into a wide range of bioactive peptides, originates from their contributions to the restriction of conformational space and the stabilization of preferential bioactive conformations that support higher efficacy and binding affinity to cognate macromolecular targets, improved specificity and lowering susceptibility to enzymatic degradation processes. Introducing CuI-catalyzed azide-alkyne cycloaddition (CuAAC), a prototypical click reaction, to the field of peptide sciences as a bio-orthogonal reaction that generates a disubstituted-[1,2,3]triazol-1-yl moiety as a pseudopeptidic bond that is peptidomimetic in nature, paved the way to its widespread application as a new and promising mode of macrocyclization. This review presents the state-of-art of CuAAC-mediated macrocyclization as it applies to an expansive range of bioactive peptides and explores the relationship among the structural diversity of CuAACmediated cyclizations, biological activities and conformations.
Export Options
About this article
Cite this article as:
Testa Chiara, Papini Maria Anna , Chorev Michael*, Rovero Paolo*, Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC)-Mediated Macrocyclization of Peptides: Impact on Conformation and Biological Activity, Current Topics in Medicinal Chemistry 2018; 18 (7) . https://dx.doi.org/10.2174/1568026618666180518095755
DOI https://dx.doi.org/10.2174/1568026618666180518095755 |
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
-
Childhood Medulloblastoma: Current Therapies, Emerging Molecular Landscape and Newer Therapeutic Insights
Current Neuropharmacology CD26: A Multi-Purpose Pharmacological Target
Current Clinical Pharmacology Methylation of ZNF331 Promotes Cell Invasion and Migration in Human Esophageal Cancer
Current Protein & Peptide Science The Pictet-Spengler Reaction Still on Stage
Current Pharmaceutical Design Human Reduced Folate Carrier Gene and Transcript Variants: Functional, Physiologic, and Pharmacologic Consequences
Current Pharmacogenomics Organosulfur Compounds in Cancer Chemoprevention
Mini-Reviews in Medicinal Chemistry Peptide-Mediated Delivery of Therapeutic and Imaging Agents Into Mammalian Cells
Current Pharmaceutical Design E2F1-Mediated Apoptosis as a Target of Cancer Therapy
Current Molecular Pharmacology The Anti-malarial Drug Artesunate Blocks Wnt/β-catenin Pathway and Inhibits Growth, Migration and Invasion of Uveal Melanoma Cells
Current Cancer Drug Targets Liposomes: An Emerging Approach for the Treatment of Cancer
Current Pharmaceutical Design PI3K/ Akt/ mTOR Pathway as a Therapeutic Target for Colorectal Cancer: A Review of Preclinical and Clinical Evidence
Current Drug Targets Specific Active Immunotherapy of Cancer: Potential and Perspectives
Reviews on Recent Clinical Trials <i>Nigella sativa</i> – A Functional Spice From A Pharaoh’s Tomb to Modern Healthcare
The Natural Products Journal Lipid-based Nanoplatforms in Cancer Therapy: Recent Advances and Applications
Current Cancer Drug Targets ABC Transporter Inhibitors in Reversing Multidrug Resistance to Chemotherapy
Current Drug Targets Epigallocatechin-3-Gallate Prevents Autoimmune-Associated Down- Regulation of p21 in Salivary Gland Cells Through a p53-Independent Pathway
Inflammation & Allergy - Drug Targets (Discontinued) Facile Eco-compactable Design for the Synthesis and Characterization of Silver Nanoparticles
Nanoscience & Nanotechnology-Asia Role of α6β4 Integrin in Cell Motility, Invasion and Metastasis of Mammary Tumors
Current Protein & Peptide Science Ultrasound-Triggered Immunotherapy for Cancer Treatment: An Update
Current Protein & Peptide Science Meeting Report The Third Annual PepTalk Meeting: The Human Proteome
Current Proteomics