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.
Graphical Abstract
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.
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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 |
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