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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC)-Mediated Macrocyclization of Peptides: Impact on Conformation and Biological Activity

Author(s): Chiara Testa, Anna Maria Papini, Michael Chorev* and Paolo Rovero*

Volume 18 , Issue 7 , 2018

Page: [591 - 610] Pages: 20

DOI: 10.2174/1568026618666180518095755

Price: $65


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.

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