French-Italian Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, University of Florence, 50019, Sesto Fiorentino, Italy.
Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy.
Curr Top Med Chem. 2018;18(7):591-610. doi: 10.2174/1568026618666180518095755.
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.
设计新型大环化模式的持久动力，以及将其应用于广泛的生物活性肽中，源于它们对构象空间的限制和对优先生物活性构象的稳定作用，这些构象支持更高的效力和与同源大分子靶标的结合亲和力、提高的特异性和降低对酶降解过程的敏感性。将 CuI 催化的叠氮-炔环加成（CuAAC）作为一种生物正交反应引入肽科学领域，该反应生成一个二取代的[1,2,3]三唑-1-基作为拟肽键，在性质上是肽模拟物，为其广泛应用作为一种新的有前途的大环化模式铺平了道路。这篇综述介绍了 CuAAC 介导的大环化作为一种广泛应用于各种生物活性肽的方法的最新进展，并探讨了 CuAAC 介导的环化的结构多样性、生物活性和构象之间的关系。
