title: Cyanohydrin as an Anchoring Group for Potent and Selective Inhibitors of Enterovirus 71 3C Protease.
abstract: Cyanohydrin derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. Compared with the reported inhibitors, cyanohydrins (1S,2S,2'S,5S)-16 and (1R,2S,2'S,5S)-16 exhibited significantly improved activity and attractive selectivity profiles against other proteases, which were a result of the specific interactions between the cyanohydrin moiety and the catalytic site of 3C(pro). Cyanohydrin as an anchoring group with high selectivity and excellent inhibitory activity represents a useful choice for cysteine protease inhibitors.
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Xiangshuai
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Zhengjie
authors.initials: Z
authors.lastname: Cui
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory of Structural Biological & Ministry of Education (MOE), and Laboratory of Protein Science, School of Medicine and Life Sciences, Tsinghua University , Beijing 100084, China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Chemistry, and Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Central China Normal University , Wuhan 430079, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Debin
authors.initials: D
authors.lastname: Zeng
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science , Beijing 100101, China.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Laboratory of Structural Biological & Ministry of Education (MOE), and Laboratory of Protein Science, School of Medicine and Life Sciences, Tsinghua University , Beijing 100084, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lou
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Luqing
authors.initials: L
authors.lastname: Shang
authors.affiliation: College of Pharmacy and State Key Laboratory of Elemento-Organic Chemistry, Nankai University , 94 Weijin Road, Nankai District, Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D029821:Enterovirus A, Human / Q000187:drug effects* / Q000201:enzymology*; D004769:Enterovirus Infections / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D062105:Molecular Docking Simulation; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D009570:Nitriles; D014764:Viral Proteins; C430593:cyanohydrin; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases