刘磊 - 清华大学

个人简介

1995 - 1999 中国科学技术大学，本科 1999 - 2004 Columbia University，博士 2004 - 2007 Scripps Research Institute，博士后

研究领域

We are developing a comprehensive method system to implement de novo chemical synthesis of any proteins found in nature or artificially designed, without limitation of the building block structure or chirality. This method system allows us to address fundamental biochemical questions, such as elucidation of how enzymes selectively making or breaking chemical bonds on complex protein substrates, and create novel functional molecules, such as synthetic protein-based self-amplification and self-replication systems.

近期论文

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Synthetic E2-Ub-nucleosome conjugates for studying nucleosome ubiquitination. Huasong Ai, Zebin Tong, Zhiheng Deng, Jiakun Tian, Liying Zhang, Maoshen Sun, Yunxiang Du, Ziyu Xu, Qiang Shi, Lujun Liang, Qingyun Zheng, Jia-Bin Li, Man Pan*, Lei Liu*. Chem, 2023, 9, 1-20. https://doi.org/10.1016/j.chempr.2023.01.012 Single-Shot Solid-Phase Synthesis of Full-Length H2 Relaxin Disulfide Surrogates. Rui Zhao, Pan Shi, Ji-bin Cui, Chaowei Shi, Xiao-Xiong Wei, Jie Luo, Zhemin Xia, Wei-Wei Shi, Yingxin Zhou, Jiahui Tang, Changlin Tian, Mark Meininghaus, Donald Bierer, Jing Shi, Yiming Li, Lei Liu*. Angew. Chem. Int. Ed., 2023, 62, e202216365. https://doi.org/10.1002/anie.202216365 Chemical synthesis of post-translationally modified H2AX reveals redundancy in interplay between histone phosphorylation, ubiquitination, and methylation on the binding of 53BP1 with nucleosomes. Huasong Ai, Guo-Chao Chu, Qingyue Gong, Ze-Bin Tong, Zhiheng Deng, Xin Liu, Fan 5Yang, Ziyu Xu, Jia-Bin Li*, Changlin Tian*, Lei Liu*. J. Am. Chem. Soc., 2022, 144, 18329-18337. https://doi.org/10.1021/jacs.2c06156 Expedient synthesis of ubiquitin-like protein ISG15 tools through chemo-enzymatic ligation catalyzed by a viral protease Lbpro. Tian Wang, Chuntong Li, Meijing Wang, Jiachen Zhang, Qingyun Zheng, Lujun Liang, Guochao Chu, Xiaolin Tian, Haiteng Deng, Wei He*, Lei Liu*, Jinghong Li*. Angew. Chem. Int. Ed., 2022, e202206205. https://doi.org/10.1002/anie.202206205 Recent progress in dissecting ubiquitin signals with chemical biology tools. Qingyun Zheng, Zhen Su, Yuanyuan Yu*, Lei Liu*. Curr. Opin. Chem. Biol., 2022, 70, 102187. https://doi.org/10.1016/j.cbpa.2022.102187 H2B Lys34 ubiquitination induces nucleosome distortion to stimulate Dot1L activity. Huasong Ai, Maoshen Sun, Aijun Liu, Zixian Sun, Tingting Liu, Lin Cao, Lujun Liang, Qian Qu, Zichen Li, Zhiheng Deng, Zebin Tong, Guochao Chu, Xiaolin Tian, Haiteng Deng, Suwen Zhao, Jia-Bin Li*, Zhiyong Lou*, Lei Liu*. Nat. Chem. Biol., 2022, 18, 972-980. https://doi.org/10.1038/s41589-022-01067-7 Structural insights into the activation of somatostatin receptor 2 by cyclic SST analogues. Qing Bo, Fan Yang, Yingge Li, Xianyu Meng, Huanhuan Zhang, Yingxin Zhou, Shenglong Ling, Demeng Sun, Pei Lv, Lei Liu*, Pan Shi* & Changlin Tian*. Cell Discov., 2022, 8, 47. https://doi.org/10.1038/s41421-022-00405-2 Thioester-assisted Sortase-A – mediated ligation. Chong Zuo, Ruichao Ding, Xiangwei Wu, Yuanxia Wang, Guo-Chao Chu, Lu-Jun Liang, Huasong Ai, Ze-Bin Tong, Junxiong Mao, Qingyun Zheng, Tian Wang, Zichen Li, Lei Liu*, Demeng Sun*. Angew. Chem. Int. Ed., 2022, 61, e202201887. https://doi.org/10.1002/anie.202201887 Structural insights into thyrotropin-releasing hormone receptor activation by an endogenous peptide agonist or its orally administered analogue. Fan Yang, Huanhuan Zhang, Xianyu Meng, Yingge Li, Yingxin Zhou, Shenglong Ling, Demeng Sun, Pei Lv, Lei Liu*, Pan Shi*, Changlin Tian*. Cell Research, 2022, 32, 858861. https://doi.org/10.1038/s41422-022-00646-6 Total chemical synthesis of correctly folded disulfide-rich proteins using a removable O-linked β-N-acetylglucosamine strategy. Wei-Wei Shi, Chaowei Shi, Tong-Yue Wang, Yu-Lei Li, Yong-Kang Zhou, Xu-Han Zhang, Donald Bierer, Ji-Shen Zheng*, Lei Liu*. J. Am. Chem. Soc., 2022, 144, 349-357. https://doi.org/10.1021/jacs.1c10091 Structural insights into Ubr1-mediated N-degron polyubiquitination. Man Pan*, Qingyun Zheng, Tian Wang, Lujun Liang, Junxiong Mao, Chong Zuo, Ruichao Ding, Huasong Ai, Yuan Xie, Dong Si, Yuanyuan Yu*, Lei Liu*, Minglei Zhao*. Nature, 2021, 600, 334-338. https://doi.org/10.1038/s41586-021-04097-8 Chemical synthesis of a full-length G‐protein-coupled receptor β2‐adrenergic receptor with defined modification patterns at the C‐terminus. Yulei Li, Jie Heng, Demeng Sun, Baochang Zhang, Xin Zhang, Yupeng Zheng, Wei-Wei Shi, Tong-Yue Wang, Jiu-Yi Li, Xiaoou Sun, Xiangyu Liu, Ji-Shen Zheng*, Brian K. Kobilka, Lei Liu*. J. Am. Chem. Soc., 2021, 143, 17566-17576. https://doi.org/10.1021/jacs.1c07369 Use of a removable backbone modification strategy to prevent aspartimide formation in the synthesis of Asp lactam cyclic peptides. Tingting Cui, Junyou Chen, Rui Zhao, Yanyan Guo, Jiahui Tang, Yulei Li, Yi-Ming Li*, Donald Bierer, Lei Liu*. Chin. J. Chem., 2021, 39, 2517-2522. http://dx.doi.org/10.1002/cjoc.202100272 Mechanistic insight into substrate processing and allosteric inhibition of human p97. Man Pan, Yuanyuan Yu, Huasong Ai, Qingyun Zheng, Yuan Xie, Lei Liu*, Minglei Zhao*. Nat. Struct. Mol. Biol., 2021, 28, 614-625. https://doi.org/10.1038/s41594-021-00617-2 K29-linked ubiquitin signaling regulates proteotoxic stress response and cell cycle. Yuanyuan Yu, Qingyun Zheng, Satchal K. Erramilli, Man Pan, Seongjin Park, Yuan Xie, Jingxian Li, Jingyi Fei, Anthony A. Kossiakoff*, Lei Liu*, Minglei Zhao*. Nat. Chem. Biol., 2021, 17, 896-905. https://doi.org/10.1038/s41589-021-00823-5 Chemical synthesis of activity-based E2-ubiquitin probes for the structural analysis of E3 ligase-catalyzed transthiolation. Lu-Jun Liang, Guo-Chao Chu, Qian Qu, Chong Zuo, Junxiong Mao, Qingyun Zheng, Jingnan Chen, Xianbin Meng, Yangwode Jing, Haiteng Deng, Yi-Ming Li, Lei Liu*. Angew. Chem. Int. Ed., 2021, 60, 17171-17177. https://doi.org/10.1002/anie.202105870 A mirror-image protein-based information barcoding and storage technology. Ji-Shen Zheng, Jun Liang, Wei-Wei Shi, Ying Li, Hong-Gang Hu, Chang-Lin Tian, Lei Liu*. Science Bulletin, 2021, 66, 1542-1549. https://doi.org/10.1016/j.scib.2021.03.010 Structural basis of human α7 nicotinic acetylcholine receptor activation. Yue Zhao, Sanling Liu*, Yingxin Zhou, Mengge Zhang, Haopeng Chen, H. Eric Xu, Demeng Sun*, Lei Liu*, Changlin Tian*. Cell Research, 2021, 31, 713-716. https://doi.org/10.1038/s41422-021-00509-6 Structural mechanism of cooperative activation of the human calcium-sensing receptor by Ca2+ ions and L-tryptophan. Shenglong Ling, Pan Shi, Sanling Liu, Xianyu Meng, Yingxin Zhou, Wenjing Sun, Shenghai Chang, Xing Zhang, Longhua Zhang, Chaowei Shi, Demeng Sun*, Lei Liu*, Changlin Tian*. Cell Research, 2021, 31, 383-394. https://doi.org/10.1038/s41422-021-00474-0 Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative. Man Pan, Qingyun Zheng, Yuanyuan Yu, Huasong Ai, Yuan Xie, Xin Zeng, Chu Wang, Lei Liu*, Minglei Zhao*. Nat. Commun., 2021, 12, 121. https://doi.org/10.1038/s41467-020-20359-x Chemical synthesis of proteins containing 300 amino acids. Baochang Zhang, Yulei Li, Weiwei Shi, Tongyue Wang, Feng Zhang, Lei Liu*. Chemical Research in Chinese Universities, 2020, 36, 733-747. https://doi.org/10.1007/s40242-020-0150-y Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1. Demeng Sun, Sanling Liu, Siyu Li, Mengge Zhang, Fan Yang, Ming Wen, Pan Shi, Tao Wang, Man Pan, Shenghai Chang, Xing Zhang, Longhua Zhang*, Changlin Tian*, Lei Liu*. eLife, 2020, 9: e57096. https://doi.org/10.7554/eLife.57096 Development and application of ubiquitin-based chemical probes. Xin Sui, Yu Wang, Yun-Xiang Du, Lu-Jun Liang, Qingyun Zheng, Yi-Ming Li*, Lei Liu*. Chem. Sci., 2020, 11, 12633-12646. https://doi.org/10.1039/D0SC03295F A diaminodiacid (DADA) strategy for the development of disulfide surrogate peptides. Yun-Kun Qi, Qian Qu, Donald Bierer, Lei Liu*. Chem. Asian J., 2020, 15, 2793-2802. https://doi.org/10.1002/asia.202000609 An E1-catalyzed chemoenzymatic strategy to isopeptide-N-ethylated deubiquitylase-resistant ubiquitin probes. Qingyun Zheng, Tian Wang, Guo-Chao Chu, Chong Zuo, Rui Zhao, Xin Sui, Linzhi Ye, Yuanyuan Yu, Jingnan Chen, Xiangwei Wu, Wenhao Zhang, Haiteng Deng, Jing Shi, Man Pan*, Yi-Ming Li*, Lei Liu*. Angew. Chem. Int. Ed., 2020, 59, 13496-13501. https://doi.org/10.1002/anie.202002974 A novel D-peptide identified by mirror-image phage display blocks TIGIT/PVR for cancer immunotherapy. Xiuman Zhou, Chao Zuo, Wanqiong Li, Weiwei Shi, Xiaowen Zhou, Hongfei Wang, Shaomeng Chen, Jiangfeng Du, Guanyu Chen, Wenjie Zhai, Wenshan Zhao, Yahong Wu, Yuanming Qi, Lei Liu*, Yanfeng Gao*. Angew. Chem. Int. Ed., 2020, 59, 15114-15118. https://doi.org/10.1002/anie.202002783 Advances on structural mechanisms of ubiquitinated nucleosome complexes. Ziyu Xu, Huasong Ai, Maoshen Sun, Jiakun Tian, Lei Liu*. Sci. Sin. Chim., 2020, 50, 415-436. http://engine.scichina.com/publisher/scp/journal/SSC/50/4/10.1360/SSC-2019-0170?slug=fulltext Synthesis of disulfide surrogate peptides incorporating large-span surrogate bridges through a native-chemical-ligation-assisted diaminodiacid strategy. Qian Qu, Shuai Gao, Fangming Wu, Meng-Ge Zhang, Ying Li, Long-Hua Zhang, Donald Bierer, Chang-Lin Tian*, Ji-Shen Zheng*, Lei Liu*. Angew. Chem. Int. Ed., 2020, 59, 6037-6045. https://doi.org/10.1002/anie.201915358 Identification of interferon receptor IFNAR2 as a novel HCV entry factor by using chemical probes. Jie Qing, Ming Wu, Rui Luo, Jizheng Chen, Lin Cao, Debin Zeng, Luqing Shang, Junxiu Nong, Qinkai Wu, Bi-Sen Ding, Xinwen Chen*, Zihe Rao*, Lei Liu*, Zhiyong Lou*. ACS Chem. Biol., 2020, 15, 1232-1241. https://doi.org/10.1021/acschembio.9b00912 Inactivity of YGL082W in vitro due to impairment of conformational change in the catalytic center loop. Lining Lu, Yu Guo, Tian Wang, Lujun Liang, Suwen Zhao*, Feng Wang*, Lei Liu*. Sci. China Chem., 2020, 63, 237-243. https://link.springer.com/article/10.1007%2Fs11426-019-9623-0 Chemical protein synthesis enabled mechanistic studies on the molecular recognition of K27-linked ubiquitin chains. Man Pan, Qingyun Zheng, Shan Ding, Lujia Zhang, Qian Qu, Tian Wang, Danning Hong, Yujing Ren, Lujun Liang, Chunlai Chen*, Ziqing Mei*, Lei Liu*. Angew. Chem. Int. Ed., 2019, 58, 2627-2631. https://doi.org/10.1002/anie.201810814 Cysteine-aminoethylation-assisted chemical ubiquitination of recombinant histones. Guo-Chao Chu, Man Pan, Jiabin Li, Sanling Liu, Chong Zuo, Ze-Bin Tong, Jing-Si Bai, Qingyue Gong, Huasong Ai, Jian Fan, Xianbin Meng, Yi-Chao Huang, Jing Shi, Haiteng Deng, Changlin Tian*, Yi-Ming Li*, Lei Liu*. J. Am. Chem. Soc., 2019, 141, 3654-3663. https://doi.org/10.1021/jacs.8b13213 Examination of the deubiquitylation site selectivity of USP51 by using chemically synthesized ubiquitylated histones. Huasong Ai, Yu Guo, Demeng Sun, Sanling Liu, Yunkun Qi, Jing Guo, Qian Qu, Qingyue Gong, Suwen Zhao*, Jiabin Li*, Lei Liu*. ChemBioChem, 2019, 20, 221-229. https://doi.org/10.1002/cbic.201800432 Chemical synthesis of structurally de?ned phosphorylated ubiquitins suggests impaired Parkin activation by phosphorylated ubiquitins with a non-phosphorylated distal unit. Man Pan, Qingyun Zheng, Shuai Gao, Qian Qu, Yuanyuan Yu, Ming Wu, Huan Lan, Yulei Li, Sanling Liu, Jiabin Li, Demeng Sun, Lining Lu, Tian Wang, Wenhao Zhang, Jiawei Wang, Yiming Li, Hong-Gang Hu*, Changlin Tian*, Lei Liu*. CCS Chem., 2019, 1, 476-489. https://doi.org/10.31635/ccschem.019.20190001 Chimeric protein probes for C5a receptors through fusion of the anaphylatoxin C5a core region with a small-molecule antagonist. Chao Zuo, Wei-Wei Shi, Xiao-Xu Chen, Marie Glatz, Bernd Riedl, Ingo Flamme, Elisabeth Pook, Jiawei Wang, Ge-Min Fang, Donald Bierer, Lei Liu*. Sci. China Chem., 2019, 62, 1371-1378. https://link.springer.com/article/10.1007/s11426-019-9513-2 Ligation of soluble but unreactive peptide segments in the chemical synthesis of Haemophilus influenzae DNA ligase. Baochang Zhang, Qiang Deng, Chong Zuo, Bingjia Yan, Chao Zuo, Xiu-Xiu Cao, Ting F. Zhu, Ji-Shen Zheng*, Lei Liu*. Angew. Chem. Int. Ed., 2019, 58, 12231-12237. https://doi.org/10.1002/anie.201905149 Chemical synthesis of proteins that cannot be obtained recombinantly. Lei Liu*. Isr. J. Chem., 2019, 59, 64-70. https://doi.org/10.1002/ijch.201800135 Selective modification of natural nucleophilic residues in peptides and proteins using arylpalladium complexes. Wan-Min Cheng, Xi Lu, Jing Shi*, Lei Liu*. Org. Chem. Front., 2018, 5, 3186-3193. https://doi.org/10.1039/C8QO00765A Acyl donors for native chemical ligation. Bingjia Yan, Weiwei Shi, Linzhi Ye, Lei Liu*. Curr. Opin. Chem. Biol., 2018, 46, 33-40. https://doi.org/10.1016/j.cbpa.2018.03.018 Studies on mirror-image proteins. Zichen Li, Baochang Zhang, Chong Zuo, Lei Liu*. Chin. J. Org. Chem., 2018, 38, 2412-2419. http://sioc-journal.cn/Jwk_yjhx/CN/10.6023/cjoc201804014 Semi-synthesis of disulfide-linked branched tri-ubiquitin mimics. Yanyan Si, Lujun Liang, Shan Tang, Yunkun Qi, Yong Huang, Lei Liu*. Sci. China Chem., 2018, 61, 412-417. https://link.springer.com/article/10.1007%2Fs11426-017-9189-6 Cryo-EM structure of the ASIC1a-mambalgin-1 complex reveals that the peptide toxin mambalgin-1 inhibits acid-sensing ion channels through an unusual allosteric effect. Demeng Sun, You Yu, Xiaobin Xue, Man Pan, Ming Wen, Siyu Li, Qian Qu, Xiaorun Li, Longhua Zhang, Xueming Li, Lei Liu*, Maojun Yang*, Changlin Tian*. Cell Discov., 2018, 4, 27. https://doi.org/10.1038/s41421-018-0026-1 Chemical synthesis of membrane proteins by the removable backbone modification method. Shan Tang, Chao Zuo, Dong-Liang Huang, Xiao-Ying Cai, Long-Hua Zhang, Chang-Lin Tian*, Ji-Shen Zheng*, Lei Liu*. Nat. Protoc., 2017, 12, 2554-2569. https://doi.org/10.1038/nprot.2017.129 Mirror-image polymerase chain reaction. Wenjun Jiang, Baochang Zhang, Chuyao Fan, Min Wang, Jiaxing Wang, Qiang Deng, Xianyu Liu, Ji Chen, Jishen Zheng, Lei Liu*, Ting F Zhu*. Cell Discov., 2017, 3, 17037. https://doi.org/10.1038/celldisc.2017.37 Recent advances in racemic protein crystallography. Bingjia Yan, Linzhi Ye, Weiliang Xu, Lei Liu*. Bioorg. Med. Chem., 2017, 25, 4953-4965. https://doi.org/10.1016/j.bmc.2017.05.020 Total chemical synthesis of a thermostable enzyme capable of polymerase chain reaction. Weiliang Xu, Wenjun Jiang, Jiaxing Wang, Linping Yu, Ji Chen, Xianyu Liu, Lei Liu*, Ting F Zhu*. Cell Discov., 2017, 3, 17008. https://doi.org/10.1038/celldisc.2017.8 Practical chemical synthesis of atypical ubiquitin chains by using an isopeptide-linked Ub isomer. Shan Tang, Lu-Jun Liang, Yan-Yan Si, Shuai Gao, Jia-Xing Wang, Jun Liang, Ziqing Mei*, Ji-Shen Zheng*, Lei Liu*. Angew. Chem. Int. Ed., 2017, 56, 13333-13337. https://doi.org/10.1002/anie.201708067 Removable backbone modification method for the chemical synthesis of membrane proteins. Jia-Bin Li, Shan Tang, Ji-Shen Zheng*, Chang-Lin Tian*, Lei Liu*. Acc. Chem. Res., 2017, 50, 1143-1153. https://doi.org/10.1021/acs.accounts.7b00001