title: An in-tether sulfoxide chiral center influences the biophysical properties of the N-capped peptides.
abstract: Thanks to their large binding interfaces, peptides are attractive ligands targeting protein-protein interactions compared with small molecules. Various strategies to improve peptides' pharmaceutical properties have been developed to constrain peptides into their functional three-dimensional structures. In our previous work, we reported that an in-tether chiral center could modulate peptides' biophysical properties. Herein, we applied this concept to construct a chiral sulfoxide center into the N-terminal end-cap system. We proved that this in-tether sulfoxide chiral center influences the structure of this N-capped template. In addition, longer peptides targeting estrogen receptor were also synthesized and we revealed that this chiral center could also modulate binding affinity to estrogen receptor alpha with enhanced protease resistance.
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, PR China.
authors.forename: Jingxu
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 611756, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, PR China.
authors.forename: Dongyuan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Gynecology, The Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, PR China. Electronic address: szyxy2009@hotmail.com.
authors.forename: Xiyang
authors.initials: X
authors.lastname: Ye
authors.affiliation: School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, PR China. Electronic address: lizg@pkusz.edu.cn.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Li
mesh_terms: D001703:Biophysics; D002851:Chromatography, High Pressure Liquid; D047628:Estrogen Receptor alpha / Q000737:chemistry; D008024:Ligands; D009842:Oligopeptides / Q000737:chemistry*; D013237:Stereoisomerism; D013454:Sulfoxides / Q000737:chemistry*
chemical_list: D047628:Estrogen Receptor alpha; D008024:Ligands; D009842:Oligopeptides; D013454:Sulfoxides
keywords: Cyclic peptide; Estrogen receptor alpha; N terminal end-cap; Sulfoxide chiral center