摘要
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.
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.
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)
作者简介
Yang Jiang is a principle investigator at Chengdu University in Sichuan. China. His lab focuses on develop- ing peptides and peptidomimetics as drug candidates and chemical biology tools. He received his B.S. and Ph.D. from Tsinghua University. The postgraduate work was on peptide synthesis and phosphorylation with Prof. Yufen Zhao. He had been postdoctoral researcher in Stockholm University and University of Oslo working on cell- penetrating peptides and caspase inhibitors. Before joining Chengdu University, he had worked in pharma- ceutical industry as project and department leader on peptide and small molecule drug discovery programs.jiangyang@cdu.edu.cn
