Cyclic and Macrocyclic Peptides as Chemical Tools To Recognise Protein Surfaces and Probe Protein-Protein Interactions.
Cyclic and Macrocyclic Peptides as Chemical Tools To Recognise Protein Surfaces and Probe Protein-Protein Interactions.
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DOI：
10.1002/cmdc.201500450
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发表时间：
2016-04-19
期刊：
影响因子：
3.4
通讯作者：
Ciulli A
中科院分区：
文献类型：
--
作者：
Cardote TA;Ciulli A
用小分子靶向蛋白质表面和蛋白质-蛋白质相互作用（PPI）是化学生物学的前沿目标，并为药物发现提供了有吸引力的治疗机会。蛋白质表面的分子特性，包括其浅特征和缺乏深结合口袋，构成了重大挑战，因此已被证明难以靶向。肽是这一使命的理想候选者，因为它们能够密切模拟蛋白质界面的许多结构特征。然而，它们固有的低细胞内稳定性和渗透性以及高体内清除率迄今限制了它们的生物学应用。改善这些性质的一种方法是通过环化来限制线性肽的二级结构。本文综述了近年来作为蛋白质表面化学探针和PPI调节剂的各类环肽和大环肽。对该领域日益增长的兴趣和最新进展提供了证据，证明开发专门针对这些相互作用的肽样分子的潜力。
Targeting protein surfaces and protein–protein interactions (PPIs) with small molecules is a frontier goal of chemical biology and provides attractive therapeutic opportunities in drug discovery. The molecular properties of protein surfaces, including their shallow features and lack of deep binding pockets, pose significant challenges, and as a result have proved difficult to target. Peptides are ideal candidates for this mission due to their ability to closely mimic many structural features of protein interfaces. However, their inherently low intracellular stability and permeability and high in vivo clearance have thus far limited their biological applications. One way to improve these properties is to constrain the secondary structure of linear peptides by cyclisation. Herein we review various classes of cyclic and macrocyclic peptides as chemical probes of protein surfaces and modulators of PPIs. The growing interest in this area and recent advances provide evidence of the potential of developing peptide‐like molecules that specifically target these interactions.