title: Self-assembling choline mimicks with enhanced binding affinities to C-LytA protein.
abstract: Streptococcus pneumoniae (pneumococcus) causes multiple illnesses in humans. Exploration of effective inhibitors with multivalent attachment sites for choline-binding modules is of great importance to reduce the pneumococcal virulence. In this work, we successfully developed two self-assembling choline mimicks, Ada-GFFYKKK' and Nap-GFFYKKK', which have the abilities to self-assemble into nanoparticles and nanofibers, respectively, yielding multivalent architectures. Additionally, the best characterized choline-binding module, C-terminal moiety of the pneumococcal cell-wall amidase LytA (C-LytA) was also produced with high purity. The self-assembling Ada-GFFYKKK' and Nap-GFFYKKK' show strong interactions with C-LytA, which possess much higher association constant values to the choline-binding modules as compared to the individual peptide Fmoc-K'. This study thus provides a self-assembly approach to yield inhibitors that are very promising for reducing the pneumococcal virulence.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Long
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China.
authors.forename: Zhimou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ding
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D032701:Biomimetics; D002473:Cell Wall / Q000201:enzymology; D002794:Choline / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D057139:Nanofibers / Q000008:administration & dosage / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000472:pathogenicity
chemical_list: D000581:Amidohydrolases; C019665:amidase; D002794:Choline