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个人简介

was born in China. He received his B.Sc. with honors from Ohio State University (USA) in 1993 and his PhD from Purdue University (USA) in 1998. His PhD research involved Bioorganic Chemistry and de novo peptide & protein design, working under the supervision of Prof. Jean A. Chmielewski. After obtaining a fellowship from CRI (Cancer Research Institute, USA) in 1998, he carried out his post-doctoral research first at University of California, Berkeley, then at Scripps Research Institute (USA), both under the supervision of Prof. Peter G Schultz. His current research interests include Combinatorial Chemistry, Chemical Biology & Functional Genomics. He joined NUS in March, 2001 as an assistant professor in Department of Chemistry & Department of Biological Sciences, and promoted to Associate Professor on Jan 1, 2006. He becomes Full Professor in 2011. He was the Dean’s Chair Professor from 2009-2012.

研究领域

A key step towards the biological characterization of enzymes, as well as their adoption as drug targets, is the development of global solutions that bridge the gap in understanding these proteins and their interactions. We herein present technological advances that facilitate the study of enzymes and their properties in a high-throughput manner. Over the years, our group has introduced and developed a variety of such enabling platforms for many classes of enzymes, including kinases, phosphatases and proteases. For each of these different types of enzymes, specific design considerations are required to develop the appropriate chemical tools to characterize each class. These tools include activity-based probes and chemical compound libraries, which are rapidly assembled using efficient combinatorial synthesis or “click chemistry” strategies. The resulting molecular assortments may then be screened against the target enzymes in high-throughput using microplates or microarrays. These techniques offer powerful means to study, profile, and discover potent small molecules that can modulate enzyme activity.

近期论文

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Cell-Active Irreversible Covalent Inhibitors that Chemoselectively Target Drug-Resistant TRKAG595R and ALKG1202R Kinase Mutants xxxx (2024), in preparation. Zuqun Wang, Xuan Wang, Jiahuan He, Lu Wang, Yan Zhang, Xiaojuan Song, Fang Yang, Shenjie Huang, Yang Zhou, Zhengchao Tu, Liqian Gao, Zhang Zhang,* Zhi-Min Zhang,* Shao Q. Yao,* Xiaoyun Lu* Tumor Microenvironment-Responsive Self-Assembled Nanomedicine for Covalent Targeting of BCR-ABL Kinase xxxx (2024), in preparation. Menghua Xiang, Fen Yang, Peng Chen, Jiaoyu Chen, Jianzhong Zhang, Jiayi Yang, Yilin Liu, Qianqian Zhang, Jiang Pi,* Peiyan Yuan,* Shao Q. Yao,* Liqian Gao,* Comparative studies of catalytic lysine-targeting covalent strategies in the human kinome. xxxx. (2024), submitted. Guanghui Tang,† Xuan Wang,† Fengfei Miao,† Huisi Huang, Manyi Xu, Chong-Jing Zhang, Liqian Gao, Zhi-Min Zhang,* Shao Q. Yao,* Xiaoyun Lu* Cell-Active, Arginine-Targeting Irreversible Covalent Inhibitors for Protein Kinases and Non-Kinases xxxxx (2024), submitted. Peng Chen, Jie Sun, Lu Wang, Menghua Xiang, Mingxi Gu, Xuan Wang, Fengfei Miao, Peiyan Yuan, Zhi-Min Zhang,* Xiaoyun Lu,* Liqian Gao,* Shao Q. Yao,* A Self-Assembled Nano-Molecular Glue (Nano-mGlu) Enables GSH/H2O2-Triggered Targeted Protein Degradation in Cancer Therapy xxxx (2024), submitted. Jie Sun, Mingxi Gu, Lvyang Peng, Jing Guo, Peng Chen, Yalei Wen, Fang Feng, Xiaojuan Chen, Tongzheng Liu, Yongheng Chen, Xiaoyun Lu,* Liqian Gao,* Shao Q Yao,* and Peiyan Yuan* Chemical probe-enabled lipid droplet proteomics J. Am. Chem. Soc. (2024), in revision. Jing Xiang, Tao Li, Junzhe Zhang, Wenxian Wu, Guangyu Xu, Hao Wang, Suyuan Chen, Jiaqian Yan, Shao Q. Yao, Miaomiao Wang,* Fan Yi,* Jigang Wang,* Yusheng Xie* PROTAC-Based Degradation of Catechol-O-Methyltransferase for Potential Treatment of Parkinson’s Disease Angew. Chem. Int. Ed. (2024), in revision. Haixiao Fang, Panpan Li, Shubo Du, Jing Gu, Xia Liu, Bo Peng, Cheng-wu Zhang, Hua Bai, Kai Huang, Lin Li,* Shao Q. Yao,* Wei Huang* Chemical Evolution to Improve Bcr-Abl Kinase Inhibitors via Covalent and Pro-/Dual-drug Targeting Strategies J. Adv. Res. (2024), in revision. Jie Sun, Liang Lou, Chengjun Zhu, Peng Chen, Guanghui Tang, Mingxi Gu, Shu Xia, Xiao Dong,* Zhi-Min Zhang,* Liqian Gao,* Shao Q. Yao,* Qicai Xiao* Small Molecule-Induced Posttranslational Acetylation of Catalytic Lysine of Kinases in Mammalian Cells J. Am. Chem. Soc. (2024), 146, 23978–23988. Guanghui Tang,* Xuan Wang, Huisi Huang, Manyi Xu, Xingyu Ma, Fengfei Miao, Xiaoyun Lu, Chong-Jing Zhang, Liqian Gao, Zhi-Min Zhang,* Shao Q. Yao* (Suppl Info 1) (Suppl Info 2) Reactivity-Tunable Fluorescent Platform for Selective and Biocompatible Modification of Cysteine or Lysine Adv. Sci. (2024), 11, 2402838. Xiaojie Ren, Haokun Li, Hui Peng, Yang Yang, Hang Su, Chen Huang, Xuan Wang, Jie Zhang, Zhiyang Liu, Wenyu Wei, Ke Cheng, Zhenpin Lu, Zhengqiu Li, Qian Zhao, Benzhong Tang, Shao Q. Yao,* Xiangzhi Song,* and Hongyan Sun* (Suppl Info 1) (Suppl Info 2) Kinase Inhibition via Small Molecule-Induced Intramolecular Protein Cross-Linking Angew. Chem. Int. Ed. (2024), 63, e202404195 Xuan Wang, Jie Sun, Huisi Huang, Guanghui Tang, Peng Chen, Menghua Xiang, Lin Li, Zhi-Min Zhang,* Liqian Gao,* Shao Q. Yao* (Suppl Info 1) (Suppl Info 2) Prodrug-Conjugated Tumor-Seeking Commensals for Targeted Cancer Therapy Nat. Commun. (2024), 15, 4343. Haosheng Shen, Changyu Zhang, Kwok Soon Wun, Jing Liu, Saravanan Prabhu Nadarajan, Cheng Weng, Hua Ling, Joshua K Tay, De Yun Wang, Shao Q. Yao, In Young Hwang,* Yung Seng Lee, Matthew Wook Chang* (Suppl Info 1) Targeted Degradation of Cell-Surface Proteins via Chaperone-Mediated Autophagy by Using Peptide-Conjugated Antibodies Angew. Chem. Int. Ed. (2024), 63, e202319232. Jinning Shao, Xuefen Lin, Chuhan Zhao, Shao Q. Yao, Jingyan Ge, Su Zeng, Linghui Qian* (Suppl Info 1) Global Reactivity Profiling of the Catalytic Lysine in Human Kinome for Covalent Inhibitor Development Angew. Chem. Int. Ed. (2024), 63, e202316394 Guanghui Tang,* Wei Wang, Chengjun Zhu, Huisi Huang, Peng Chen, Xuan Wang, Manyi Xu, Jie Sun, Chong-Jing Zhang, Qicai Xiao, Liqian Gao, Zhi-Min Zhang,* and Shao Q. Yao* (Suppl Info 1) (Suppl Info 2) Year 2023 Tumor Metabolism-Rewriting Nanomedicines for Cancer Immunotherapy ACS Cent. Sci. (2023), 9, 1864-1893. Xiao Dong,* Shu Xia, Shubo Du, Mao-Hua Zhu, Xing Lai, Shao Q. Yao, Hong-Zhuan Chen, and Chao Fang* Multitarget inhibitors/probes that target LRRK2 and AURORA A kinases noncovalently and covalently Chem. Commun. (2023), 59, 10789-10792. Wei Wang, Xuan Wang, Guanghui Tang,* Chengjun Zhu, Menghua Xiang, Qicai Xiao, Zhi-Min Zhang,* Liqian Gao* and Shao Q Yao* (Suppl Info) Insulin-Like Growth Factor 2 (IGF2)-fused, Lysosomal Targeting Chimeras for Degradation of Extracellular and Membrane Proteins J. Am. Chem. Soc. (2023), 145, 24272-24283. Bei Zhang, Rajeev K. Brahma, Liquan Zhu, Jiayi Feng, Shiqi Hu, Linghui Qian, Shubo Du,* Shao Q. Yao,* Jingyan Ge* (Suppl Info) Cell-Active, Irreversible Covalent Inhibitors that Selectively Target the Catalytic Lysine of EGFR by Using Fluorosulfate-Based SuFEx Chemistry Eur. J. Med. Chem. (2023), 259, 115671. Guanghui Tang, Wei Wang, Xuan Wang, Ke Ding, SoFong Cam Ngan, Jiaoyu Chen, Siu Kwan Sze, Liqian Gao, Peiyan Yuan,* Xiaoyun Lu,* Shao Q. Yao* (Suppl Info) Orthogonal Strategies for the Global Proteome Profiling of Anandamide and Cannabidiol Chem. Eur. J. (2023), 29, e202300682. Guanghui Tang, Ying-Jie Lim,* Wei Wang, Zi Ye, Chong-Jing Zhang and Shao Q. Yao* (Suppl Info 1) (Suppl Info 2) A Late-Stage Aryl C-H Olefination Strategy and Its Application Towards Global Proteome Profiling of ∆8-Tetrahydrocannabinol Chem. Eur. J. (2023), 29, e202300531. Ying-Jie Lim, Guanghui Tang, Zi Ye, Chong-Jing Zhang, Jie Wu* and Shao Q. Yao* (Suppl Info 1) (Suppl Info 2) Mitochondria-Targeted Gene Silencing Facilitated by Mito-CPDs Chem. Eur. J. (2023), 29, e202204021. Wenjie Lang, Wei Tan, Bizhong Zhou, Yuli Zhuang, Bei Zhang, Linye Jiang, Shao Q. Yao,* Jingyan Ge* (Suppl Info) The Dawn of a New Era: Targeting the ‘Undruggables’ with Antibody-Based Therapeutics Chem. Rev. (2023), 123, 7782-7853. Linghui Qian,* Xuefen Lin, Xue Gao, Rizwan Ullah Khan, Jia-Yu Liao, Shubo Du,* Jingyan Ge, Su Zeng, Shao Q. Yao* 2-Ethynylbenzaldehyde (EBA)-Based, Lysine-Targeting Irreversible Covalent Inhibitors for Protein Kinases and Non-Kinases J. Am. Chem. Soc. (2023), 145, 3844-3849. Peng Chen, Guanghui Tang,* Chengjun Zhu, Jie Sun, Xuan Wang, Menghua Xiang, Huisi Huang, Wei Wang, Lin Li, Zhi-Min Zhang,* Liqian Gao,* Shao Q Yao* (Suppl Info 1) (Suppl Info 2) Multiplex Identification of Post-translational Modifications by Deep Learning-assisted Photonic Crystal Hydrogel Sensors Angew. Chem. Int. Ed. (2023), 62, e202218412. Junjie Qin, Jia Guo, Guanghui Tang, Lin Li, Shao Q. Yao* (Suppl Info) De Novo Designed Self-assembling Rhodamine Probe for Real-time, Long-term and Quantitative Live-cell Nanoscopy ACS Nano (2023), 17, 3632-3644. Zhang, Jie; Shi, Heng; Huang, Chen; Mei, Le; Guo, Qiang; Cheng, Ke; Wu, Pingzhou; Su, Dan; Chen, Qingxin; Gan, Shenglong; Shi, Jiahai; Chen, Jianlin; Yao, Shao; Chen, Xian-Kai; Tang, Ben Zhong; He, Jufang; Sun, Hongyan* (Suppl Info) GPX4 degradation through covalent inhibitor-based PROTACs Bioorg. Chem. (2023), 134, 106461. Liquan Zhu, Shiqi Hu, Xiaoqiao Yan, Qian Zeng, Bei Zhang, Linye Jiang, Shao Q. Yao,* Jingyan Ge* (Suppl Info) Biodegradable Silica Nanocapsules Enable Efficient Nuclear-Targeted Delivery of Native Proteins for Cancer Therapy Biomaterials (2023), 294, 122000. Wei Du, Shubo Du, Xiao Dong, Hua Bai, Jiamin Jiang, Shiping Hao, Fen Yang, Qicai Xiao, Bei Zhang, Jingyan Ge, Liqian Gao, Lin Li,* Shao Q. Yao,* Wei Huang* (Suppl Info) Year 2022 Bifunctional lipid-derived affinity-based probes (AfBPs) for analysis of lipid-protein interactome Acc. Chem. Res. (2022), 55, 3663-3674. Jingyan Ge, Shubo Du,* Shao Q. Yao* Chemical Biology Tools for of Protein Lysine Acylation Angew. Chem. Int. Ed. (2022), 61, e202200303 Yusheng Xie, Shubo Du, Zhiyang Liu, Min Liu, Zhiqiang Xu, Xiaojie Wang, Jia Xuan Kee, Fan Yi*, Hongyan Sun* and Shao Q. Yao* Cell-active, reversible and irreversible covalent inhibitors that selectively target the catalytic lysine of BCR-ABL kinase Angew. Chem. Int. Ed. (2022), 61, e202203878. Peng Chen, Jie Sun, Chengjun Zhu, Guanghui Tang*, Wei Wang, Manyi Xu, Menghua Xiang, Chong-Jing Zhang, Zhi-Min Zhang*, Liqian Gao*, Shao Q. Yao* (Suppl Info 1) (Suppl Info 2) In Vivo Targeted Delivery of Antibodies into Cancer Cells with pH-Responsive Cell-Penetrating Poly(disulfide) Chem. Commun. (2022), 58, 1314-1317. Yulong Kong, Kui Zeng, Ying Zhang, Jinning Shao, Jiaqi Yan, Jia-Yu Liao, Wenchao Wang, Xiaoyang Dai, Qinjie Weng, Shao Q. Yao, Su Zeng,* Linghui Qian* Two-photon small-molecule fluorogenic probes for visualizing endogenous nitroreductase activities from tumor tissues of a cancer patient Adv. Healthc. Mater. (2022), 11, 2200400. Changmin Yu, Shuangxi Wang, Chenchen Xu, Yang Ding, Gaobing Zhang, Qicai Xiao, Limin Wang, Bin Fang, Chibin Pu, Jingyan Ge, Liqian Gao, Naidi Yang, Qiong Wu, Jie Liu, Chengwu Zhang, Lin Li,* Shao Q. Yao* Stimuli-Responsive Self-Assembled Prodrugs in Cancer Therapy Chem. Sci. (2022), 13, 4239-4269. Xiao Dong*, Rajeev K. Brahma, Chao Fang, Shao Q. Yao* Emerging Biosensing and Transducing Techniques for Potential Applications in Point-of-Care Diagnostics Chem. Sci. (2022), 13, 2857-2876. Junjie Qin*, Wei Wang, Liqian Gao, Shao Q. Yao* CPD-based nanoquenchers (qCPDs) for self-monitoring of intracellular gene delivery Chem. Commun. (2022), 58, 1792-1795. Wenjie Lang, Shubo Du, Shuyi Wang, Dawei Hong, Liquan Zhu, Si Si Liew, Linye Jiang, Shao Q. Yao*, Jingyan Ge* A reversible microarray immobilization strategy based on thiol-quinone reaction Chin. Chem. Lett. (2022), 33, 213-216. Ling Feng, Ping Wang, Yi Feng, Jie Zhang, Qingxin Chen, Yusheng Xie , Jingdong Luo, Jiang Xia, Shao Q Yao, Hongyan Sun* Intracellular co-delivery of native antibody and siRNA for combination therapy by using biodegradable silica nanocapsules Biomaterials (2022), 281, 121376. Peiyan Yuan,* Fen Yang, Si Si Liew, Jiachang Yan, Xiao Dong, Jinfeng Wang, Shubo Du, Xin Mao, Liqian Gao, Shao Q. Yao* Clickable ZIF-8 for cell type-specific delivery of functional proteins ACS Chem. Biol. (2022), 17, 32-38. Jian Liu, Shuhong Guo, Chaonan Yuan, Jie Luo, Shubo Du, Lin Li, Linye Jiang,* Shao Q. Yao,* Jingyan Ge* A proteome-wide selective, dual-targeting covalent inhibitor of VCP/p97 AAA-ATPase Acta Pharm. Sin. B (2022), 12, 982-989. Zi Ye, Ke Wang, Xiaofeng Jin, Lianguo Chen, Hao Chen, Guanghui Tang, Shao Q. Yao, Zhiqiang Feng,* Chong-Jing Zhang*

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