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个人简介

Postdoc, ETH Zurich (2010–2012) Research Assistant, National University of Singapore (2008–2009) Ph.D., Xiamen University (2005–2010) B.S., Xiamen University (2001–2005)

研究领域

Peptide Ligands and Drugs We are developing structurally-constrained peptide ligands for proteins of potential therapeutic interest. Our interests include: 1) cyclization strategies for peptides, 2) strategies for intracellular peptide delivery, 3) screening of bioactive peptides. Oxidative Folding of Polypeptides The precise pairing of cysteine (Cys) residues is essential for the conformational folding and stabilization of many proteins and natural disulfide-rich peptides. In natural systems, precise disulfide pairing is achieved by multiple oxidation, reduction, and rearrangement steps, which is predetermined by the primary sequence of the polypeptide chains and strategically regulated by molecular chaperones and enzymes such as protein disulfide isomerase. These requisites, however, are notoriously difficult to be reconstitutedin vitrofor the synthesis of disulfide-rich/multicyclic peptides, particularly when the primary sequence has to be extensively manipulated for the development of peptide therapeutics and ligands. Thus, we are particularly interested in developing novel disulfide pairing strategies to direct the folding of peptides without protecting groups, extensive manipulation of primary sequence, and resourse to elaborate post-synthetic reactions. Our work would enable the development of novel disulfide-rich scaffolds for the design of structurally-constrained peptide ligands and drugs. Fluorescent Probes Novel fluorescent probes that are developing in our lab include: 1) FRET-based probes for deciphering thiol-mediated (thiol-disulfide) exchange reactions on the cell surface or in the endocytic pathways, 2) Fluorescent turn-on probes for the sensing and imaging of intracellular proteins.

近期论文

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Yaqi Wu‡, Cong Li‡, Shihui Fan, Yibing Zhao*, and Chuanliu Wu*, Fast and Selective Reaction of 2-Benzylacrylaldehyde with 1,2-Aminothiol for Stable N-Terminal Cysteine Modification and Peptide Cyclization, Bioconjugate Chem., 2021, 32, 2065–2072. Jun Zha, Jinjing Li, Shihui Fan, Zengping Duan, Yibing Zhao* and Chuanliu Wu*, An evolution-inspired strategy to design disulfide-rich peptides tolerant to extensive sequence manipulation, Chem. Sci., 2021, 12, 11464–11472. Shuaimin Lu‡, Yapei Wu‡, Jinjing Li, Xiaoting Meng, Chenliang Hu, Yibing Zhao, and Chuanliu Wu*, Directed Disulfide Pairing and Folding of Peptides for the De Novo Development of Multicyclic Peptide Libraries, J. Am. Chem. Soc., 2020, 142, 16285–16291. Xuejun Zheng, Weidong Liu, Ziyan Liu, Yibing Zhao, Chuanliu Wu*, Biocompatible and Rapid Cyclization of Peptides with 2,4-Difluoro-6-hydroxy-1,3,5-benzenetricarbonitrile for the Development of Cyclic Peptide Libraries, Bioconjugate Chem., 2020, 31, 2085–2091. Zirong Huang, Yapei Wu, Huilei Dong, Yibing Zhao, and Chuanliu Wu*, Design and Synthesis of Disulfide-Rich Peptides with Orthogonal Disulfide Pairing Motifs, J. Org. Chem., 2020, 85, 11475–11481. Xiaoli Zheng, Zhuoru Li, Wei Gao, Xiaoting Meng, Xuefei Li, Louis Y. P. Luk, Yibing Zhao, Yu-Hsuan Tsai*, Chuanliu Wu*, Condensation of 2-((Alkylthio)(aryl)methylene)malononitrile with 1,2-Aminothiol as a Novel Bioorthogonal Reaction for Site-Specific Protein Modification and Peptide Cyclization, J. Am. Chem. Soc., 2020, 142, 5097-5103. Jun Liu‡, Jiingjing Liang‡, Chuanliu Wu*, and Yibing Zhao*, A Doubly-Quenched Fluorescent Probe for Low-Background Detection of Mitochondrial H2O2, Anal. Chem., 2019, 91, 6902−6909. Yiwu zheng, Yang Shen, Xiaoting Meng, Yaqi Wu, Yibing Zhao*, and Chuanliu Wu*,Stabilizing p-dithiobenzyl Urethane Linkers without Rate-Limiting Self-Immolation for Traceless Drug Release, ChemMedChem, 2019, 14, 1196–1203 Huilei Dong, Xiaoting Meng, Xiaoli Zheng, Xueting Cheng, Yiwu Zheng, Yibing Zhao, Chuanliu Wu*, Design and Synthesis of Crosslink-Dense Peptides by Manipulating Regioselective Bisthioether Crosslinking and Orthogonal Disulfide Pairing, J. Org. Chem., 2019, 84, 5187−5194. Yaqi Chen‡, Jingjing Liang‡, Tao Li, Ping Lin, Yibing Zhao, Chuanliu Wu*, Interchain Doubly-Bridged α-Helical Peptides for the Development of Protein Binders, Chin. Chem. Lett., 2019, 30, 924−928. Ping Lin‡, Hongwei Yao‡, Jun Zha, Yibing Zhao, Chuanliu Wu*, Ordered and Isomerically‐Stable Bicyclic Peptide Scaffolds Constrained through Cystine Bridges and Proline Turns. ChemBioChem. 2019, 20, 1514–1518. Yizhen Yin‡, Qianran Fei‡, Weidong Liu, Zhuoru Li, Hiroaki Suga*, Chuanliu Wu*, Chemical and Ribosomal Synthesis of Topologically Controlled Bicyclic and Tricyclic Peptide Scaffolds Primed by Selenoether Formation, Angew. Chem. Int. Ed., 2019, 58, 4880–4885. Xiaoting Meng, Tao Li, Yibing Zhao, Chuanliu Wu*, CXC-Mediated Cellular Uptake of Miniproteins: Forsaking "Arginine Magic", ACS Chem. Biol., 2018, 11, 3078–3086. Mirao Zha, Ping Lin, Hongwei Yao, Yibing Zhao, Chuanliu Wu*,A Phage Display-Based Strategy for the De Novo Creation of Disulfide-Constrained and Isomer-Free Bicyclic Peptide Affinity Reagents, Chem. Commun., 2018, 54, 4029–4032. Yiwu Zheng, Xiaoting Meng, Yaqi Wu, Yibing Zhao, and Chuanliu Wu*, De Novo Design of Constrained and Sequence-Independent Peptide Scaffolds with Topologically-Formidable Disulfide Connectivities, Chem. Sci., 2018, 9, 569–575. Weidong Liu and Chuanliu Wu*, A Mini-Review and Perspective on Multicyclic Peptide Mimics of Antibodies, Chin. Chem. Lett., 2018, 29, 1063–1066. Chaoyu Li‡, Jinhong Gao‡, Jun Yi‡, Xiaguang Zhang, Xiaodan Cao, Meng Meng, Chen Wang, Yaping Huang, Sanjun Zhang, Deyin Wu, Chuanliu Wu*, Jianhua Xu, Zhongqun Tian, and Jianfeng Li*, Plasmon-Enhanced Ultrasensitive Surface Analysis Using Ag Nanoantenna, Anal. Chem., 2018, 90, 2018−2022. Weidong Liu, Yiwu Zheng, Xudong Kong, Christian Heinis, Yibing Zhao, and Chuanliu Wu*, Precisely Regulated and Efficient Locking of Linear Peptides into Stable Multicyclic Topologies through a One-Pot Reaction, Angew. Chem. Int. Ed., 2017, 56, 4458−4463 (Hot paper, featured as inside back cover). Yiwu Zheng, Zhuoru Li, Jing Ren, Weidong Liu, Yaqi Wu, Yibing Zhao, and Chuanliu Wu*, Artificial Disulfide-Rich Peptide Scaffolds with Precisely Defined Disulfide Patterns and a Minimized Number of Isomers, Chem. Sci., 2017, 8, 2547−2552 (Featured as inside front cover). Yiwu Zheng, Jing Ren, Yaqi Wu, Xiaoting Meng, Yibing Zhao, and Chuanliu Wu*, Proteolytic Unlocking of Ultrastable Twin-Acylhydrazone Linkers for Lysosomal Acid-Triggered Release of Anticancer Drugs , Bioconjugate. Chem., 2017, 28, 2620−2626. Jinghui Wang, Mirao Zha, Qianran Fei, Weidong Liu, Yibing Zhao, and Chuanliu Wu*, Peptide Macrocycles Developed from Precisely-Regulated Multiple Cyclization of Unprotected Peptides , Chem. Eur. J., 2017, 23, 15150−15155.

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