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Review
. 2021 Jun:62:82-89.
doi: 10.1016/j.cbpa.2021.02.013. Epub 2021 Mar 26.

Targeting of extracellular protein-protein interactions with macrocyclic peptides

Shota Taguchi  1 , Hiroaki Suga  2
Affiliations
Review

Targeting of extracellular protein-protein interactions with macrocyclic peptides

Shota Taguchi et al. Curr Opin Chem Biol. 2021 Jun.

Abstract

Targeting of extracellular protein-protein interactions (PPI) is emerging as a major application for de novo discovered macrocyclic peptides. Modern discovery platforms can routinely identify macrocyclic peptide ligands capable of highly selective modulation of extracellular signaling pathways; amenability to chemical synthesis and natural modularity of peptides additionally provides an avenue for their further structural elaboration, while the challenge of cell internalization can be minimized. Here, we discuss the recent progress in targeting extracellular PPIs with macrocyclic peptides by focusing on a number of recent case studies. We analyze the scope and potential limitations of the discovery systems in identifying functional macrocyclic ligands. We also highlight the recent technical advancements allowing for a more streamlined discovery pipeline and our brief perspective in this field.

Keywords: Drug discovery; Extracellular protein; Macrocyclic peptide; Protein protein interaction.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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