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Contemporary strategies for peptide macrocyclization

Nature Chemistry volume 3, pages 509–524 (2011)Cite this article

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Abstract

Peptide macrocycles have found applications that range from drug discovery to nanomaterials. These ring-shaped molecules have shown remarkable capacity for functional fine-tuning. Such capacity is enabled by the possibility of adjusting the peptide conformation using the techniques of chemical synthesis. Cyclic peptides have been difficult, and often impossible, to prepare using traditional synthetic methods. For macrocyclization to occur, the activated peptide must adopt an entropically disfavoured pre-cyclization conformation before forming the desired product. Here, we review recent solutions to some of the major challenges in this important area of contemporary synthesis.

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Figure 1: General synthetic considerations for peptide macrocyclization.
Figure 2: Conformational control to facilitate peptide macrocyclization.
Figure 3: The use of metal ions to assist in the macrocyclization of peptides.
Figure 4: Peptide macrocyclizations mediated through sulfur-containing auxiliaries.
Figure 5: Peptide lactamizations through ring contractions involving larger lactones.
Figure 6: Azide–alkyne cycloadditions in the synthesis of peptide macrocycles.
Figure 7: The use of ring-closing metathesis in the synthesis of peptide macrocycles.
Figure 8: Peptide ring closures mediated by multicomponent reactions.
Figure 9: Strategies for the development of libraries of peptide macrocycles.

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The authors are grateful to the Natural Science and Engineering Research Council of Canada for financial support.

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    Christopher J. White & Andrei K. Yudin

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White, C., Yudin, A. Contemporary strategies for peptide macrocyclization. Nature Chem 3, 509–524 (2011). https://doi.org/10.1038/nchem.1062

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