Peptide Macrocycles Developed from Precisely Regulated Multiple Cyclization of Unprotected Peptides
Peptide Macrocycles Developed from Precisely Regulated Multiple Cyclization of Unprotected Peptides
复制标题
由未保护肽的精确调控多重环化开发的肽大环化合物
DOI：
10.1002/chem.201703139
复制
发表时间：
2017-10-26
影响因子：
4.3
通讯作者：
Wu, Chuanliu
中科院分区：
文献类型：
--
作者：
Wang, Jinghui;Zha, Mirao;Wu, Chuanliu
肽类大环化合物作为蛋白质配体和抑制剂的骨架材料，具有潜在的开发潜力。肽大环化的新策略对肽类药物的设计和发现具有特别的意义。本文报道了一种设计和合成大环肽的有效策略，该策略依赖于精确调节的和有效的2，3，5，6-三氟甲腈（4F-2CN）对未保护肽的一锅环化。肽双环可以被认为是一种新型的结构超约束的肽大环，其被一个刚性的闭环部分约束，由N-末端6元环和C-末端13元环与4F-2CN的苯环稠合组成。这些新的大环肽支架将是开发大环肽抑制剂和许多蛋白质的靶向配体的有趣和有前途的支架。
Peptide macrocycles have been attractive scaffolds for the development of ligands and inhibitors to proteins, which have the potential of being developed as potent drugs. Novel strategies for peptide macrocyclization should be of particular interest to peptide drug design and discovery. Herein, an efficient strategy for designing and synthesizing macrocyclic peptides, which relies on the precisely regulated and efficient one-pot cyclization of unprotected peptides with 2,3,5,6-tetrafluoroterephthalonitrile (4F-2CN), is reported. The peptide bicycles can be considered as novel structurally hyperconstrained peptide macrocycles constrained with a rigidifying ring-closing moiety, consisting of an N-terminal 6-membered ring and C-terminal 13-membered ring fused with the benzene ring of 4F-2CN. These novel macrocyclic peptide scaffolds would be intriguing and promising scaffolds for developing macrocyclic peptide inhibitors and targeting ligands for many proteins.