Highly Efficient Strategy for Constructing New Types of Peptide Macrocycles

New methods capable of effecting cyclization, and forming novel three-dimensional structures while maintaining favourable physicochemical properties are needed to facilitate the development of cyclic peptide-based drugs that can engage challenging biological targets, such as protein–protein interactions. 

Macrocyclization is one of nature’s most powerful means to construct complex molecular architectures from simple linear precursors.

Available methods for constructing peptide macrocycles with well-defined structural features and drug-like properties are currently very limited compared with synthetic methods for small molecules.

Peng Liu and his colleagues report a highly efficient and generally applicable strategy for constructing new types of peptide macrocycles using palladium-catalyzed intramolecular C(sp3)–H arylation reactions on their newly published paper in Nature Chemistry. 

This strategy provides a powerful tool to address the long-standing challenge of size- and composition-dependence in peptide macrocyclization, and generates novel peptide macrocycles with uniquely buttressed backbones and distinct loop-type three-dimensional structures.

They hope that further exploration of this strategy will enable the discovery of novel peptide macrocycles to tackle various challenging biological targets.

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