Protein-protein interactions(PPIs) are recognized as attractive therapeutic targets. However targeting PPIs especially intracellular ones has been proven extremely difficult for conventional drug-like small molecules,...Protein-protein interactions(PPIs) are recognized as attractive therapeutic targets. However targeting PPIs especially intracellular ones has been proven extremely difficult for conventional drug-like small molecules, and biological drugs such as monoclonal antibodies have difficulty in reaching intracellular targets. Macrocyclic peptides are promising candidates of PPI regulators for their potential in combining high potency and biological stability together. Cell permeability of macrocyclic peptides may also be achieved by structural modifications or conjugation to a cell-penetrating sequence. Significant progress has been made in this research area in recent years. Important technology progress and recent examples of macrocyclic peptide PPI modulators are reviewed.展开更多
基金supported by Principle Training Program of Education Department of Sichuan Province (No. 18CZ0042)Fundamental Research Fund of Chengdu University (No. 2081916027)Undergraduate Innovation Programm of Chengdu University (Nos. CDU_CX_2018250, CDU_CX_2018251)
文摘Protein-protein interactions(PPIs) are recognized as attractive therapeutic targets. However targeting PPIs especially intracellular ones has been proven extremely difficult for conventional drug-like small molecules, and biological drugs such as monoclonal antibodies have difficulty in reaching intracellular targets. Macrocyclic peptides are promising candidates of PPI regulators for their potential in combining high potency and biological stability together. Cell permeability of macrocyclic peptides may also be achieved by structural modifications or conjugation to a cell-penetrating sequence. Significant progress has been made in this research area in recent years. Important technology progress and recent examples of macrocyclic peptide PPI modulators are reviewed.