罗贵民 分子酶学工程教育部重点实验室

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罗贵民教授 博士生导师
Email:luogm@jlu.edu.cn  
 
1961-1966:吉林大学化学系学习, 专业:物理化学和生物化学; 1966-1978:吉林大学化学系助教, 1979-1984:吉林大学分子生物学系讲师; 1985-1991:吉林大学酶工程国家重点实验室副教授; 1992-1997:吉林大学酶工程国家重点实验室教授; 1998-2005:吉林大学分子酶学程教育部重点实验室教授. 罗贵民教授完成了包括国家自然科学基金项目、国家科技部973计划和863计划项目和国家“八五”和“九五”攻关项目在内的研究工作。成果获得了教育部和公共卫生部的3项科技进步奖。 罗贵民教授作为访问学者先后于1981,1987,1995和1998年访问过美国南加利福尼亚大学、哥伦比亚大学和澳大利亚昆士兰大学执行科研项目协作研究计划。2004年2月被香港大学聘为客座教授。

研究方向
(1) 开发模拟酶的新策略,着重于抗氧化酶的人工模拟。用化学修饰、分子印迹、组合化学和蛋白质工程技术改善酶的活力、稳定性和对映体选择性。通过选择性改变酶活性部位创造新酶活性。
(2) 研究人工酶的化学生物学,探索人工酶与氧化应激引起的疾病间的相互关系及人工酶在信号传导和细胞凋亡中的作用。

成果
提出了新的模拟酶策略:先构建具有底物结合部位的受体,再将催化基团装配在底物结合部位附近,力求催化基团与底物的功能基靠近,从而像天然酶那样发挥高效催化功能。
用此策略以单克隆抗体、单链抗体、天然蛋白质和酶、短肽和环糊精等为受体,成功地构建了谷胱甘肽过氧化物酶(GPX)模拟酶,为酶的人工模拟酶提供了普遍适用的新途径。
主要成果包括:(1)设计并成功地制备了世界上第一个含硒抗体酶,其活力超过天然兔肝GPX,得到了国际学术界的认可。(2)提出从组合化学-肽库中筛选出具有底物结合部位的短肽,设计合成了具有高GPX活力高底物选择性的含硒短肽。(3) 用化学法和蛋白质工程法将天然酶转化为GPX。获得的人工酶GPX活力超过相应天然酶。(4)建立了一种生物印迹与化学诱变相结合产生人工酶的新方法, 构建了具有GPX活性的含硒生物印迹酶。(5)构建了以环糊精为模型体系的系列含硒人工酶。(6)建立了数种氧化损伤模型,在亚细胞、细胞和个体三个水平上评价了GPX模拟酶的抗氧化能力,证明了GPX模拟酶可作为抗氧化药物的前导化合物。迄今为止,已经发表论文100多篇,其中50多篇被SCI收录。这些结果被权威期刊“CHEMICAL REVIEW”大段引用和评论。CURRENT MEDICINAL CHEMISTRY期刊的主编邀请罗教授撰写了关于谷胱甘肽过氧化物酶人工模拟的综述文章。

研究课题
1. Project of Natural Science Foundation of China (20572035), Design and synthesis of small peptides to create dural functional antioxidant enzymes and their synergism investigation, Jan. 1, 2006- Dec. 31, 2008
2. Project of Research & Development Plan of High Technology in China (863 Project, 2001AA215351), Molecular reform of selenium containing abzyme and its studies on pharmacology, Jan. 1, 2001 – Dec. 31, 2005
3.The Main State Basic Research Development Program of China (“973”State Key Project, G200078102 ), Construction and function integration of the multi-component and multi-layer molecular conjugates, Oct. 1, 2000 – Sept. 30, 2005.
4.Project of Natural Science Foundation of China (20272016), Imitation of glutathione peroxidase using tellurium-containing cyclodextrin, Jan. 1, 2003 - Dec. 31, 2005.
5.Project of Natural Science Foundation of China (20072010), Imitation of glutathione peroxidase by chemically mutating a designed and synthesized small-peptide, Jan. 1, 2001 - Dec. 31, 2003.

专利
1.Preparation of selenium-containing catalytic monoclonal antibody with glutathione peroxidase activity, ZL 94102481.4
2.Application of selenium-containing cyclodextrin in treatment of cataract. ZL00133040. 
3.Preparation of selenium-containing catalytic antibody with higher activity than native glutathione peroxidase, ZL96112628.0 4.Preparation of selenium-containing papain, CN1431301A
5.Application of selenium-containing cyclodextrin in drink,  ZL 03119442.7
6.Application of selenium-containing cyclodextrin in cosmetic, CN1451369A
7.Compounds of selenium-containing cyclodextrin and their application of in drug, ZL03119443.5
8.Method of determining small molecular protein and peptide using sandwich immunosensing method, CN1480731A

代表性文章
1. Zhang K, Zang TZ, Yang W, Sun Y, Mu Y, Liu JQ, Shen JC, Luo GM, Single chain antibody displays glutathione S-transferase activity, JOURNAL OF BIOLOGICAL CHEMISTRY 281 (18): 12516-12520 MAY 5 2006
2. Dong ZY, Huang X, Mao SZ, Liang K, Liu JQ, Luo GM, Shen JC, Cyclodextrin-derived mimic of glutathione peroxidase exhibiting enzymatic specificity and high catalytic efficiency, CHEMISTRY-A EUROPEAN JOURNAL 12 (13): 3575-3579 APR 14 2006
3..Sun Y, Mu Y, Ma S, Gong P, Yan G, Liu J, Shen J, Luo G,The molecular mechanism of protecting cells against oxidative stress by 2-selenium-bridged beta-cyclodextrin with glutathione peroxidase activity. Biochim Biophys Acta. 15;1743(3):199-204,2005 (SCI, Impact factor 3.482)
4.Yu HJ, Liu JQ, Bock A, Li J, Luo GM, Shen JC,Engineering glutathione transferase to a novel glutathione peroxidase mimic with high catalytic efficiency. Incorporation of selenocysteine into a glutathione-binding scaffold using an auxotrophic expression system,J. Biol. Chem., 280(12):11930-11935,2005 (SCI, Impact factor 6.482)
5.Ye Sun, Tianyu Li, Hua Chen, Kun Zhang, Keyan Zheng, Ying Mu, Ganglin Yan, Wei Li, Jiacong Shen, and Guimin Luo ,Selenium-containing 15-mer peptides with high glutathione perox idase-like activity, J. Biol. Chem, 279 (36): 37235-37240, 2004 (SCI,Impact factor 6.482)
6.Xiaojun Ren, Per Jemth, Philip G.Board, Guimin Luo , Bengt Mannervik, Junqiu Liu, Kun Zhang, Jiacong Shen, A semisynthetic glutathione peroxiase with high catalytic efficiency: Seleoglutathione transferase, Chem.Biol., 2002, 9: 789 - 794; (SCI, Impact factor 6.129)
7.Guimin Luo , Xiaojun Ren , Junqiu Liu , Ying Mu , Jiacong Shen . Towards more efficient glutathione peroxidase mimics: Substrate recognition and catalytic group assembly. Curr. Med. Chem. 2003, 10 (13): 1151-1183. (SCI, Impact factor 4.409)
8.Xiaojun Ren, Shujuan Gao, Delin You, Hualiang Huang, Zi Liu, Ying Mu, Junqiu Liu, Yan Zhang, Ganglin Yan, Guimin Luo , Tongshu Yang, Jiacong Shen, Cloning and expressing of a single-chain catalytic antibody that acts as a glutathione peroxidase mimic with high catalytic efficiency, Biochem. J., 2001, 359(2): 369 - 374; (SCI, Impact factor 4.101)
9.Xiaojun Ren, Yan Xue, Junqiu Liu, Kun Zhang, J. Zheng, Guimin Luo , C. Guo, Ying Mu, Jiacong Shen, A novel cyclodextrin-derived tellurium compound with glutathione peroxidase activity, ChemBioChem , 2002, 3:356 - 363; (SCI, Impact factor 3.992)
10.Xiaojun Ren, Yan Xue, Kun Zhang, Junqiu Liu, Guimin Luo , Jiacong Shen, A novel dicyclodextrinyl ditelluride compound with antioxidant activity, FEBS Lett . 2001, 507(3), 377 - 380; (SCI, Impact factor 3.609)
11.Guimin Luo , Danhua Qi, Yingguang Zheng, Ying Mu, Gangling Yan, Tongshu Yang and Jiacong Shen, ESR studies on reaction of saccharide with the free radicals generated from the xanthine oxidase/hypoxanthine system containing iron, FEBS lett . , 2001, 492(1-2): 29 - 32; (SCI, Impact factor 3.609)
12.Ye Sun, Ying Mu, Shumei Ma, Pingsheng Gong, Ganglin Yan, Junqiu Liu , Jiuqiu Liu , Jiacong Shen , Guimin Luo , The molecular mechanism of protecting cells against oxidative stress by 2-selenium bridged β-cyclodextrin with glutathione peroxidase activity , BBA-Mol Cell Res , 2005, 1743: 199– 204; (SCI, Impact factor 3.482)
13.Delin You, Xiaojun Ren , Yan Xue, Guimin Luo , Tongshu Yang, Jiacong Shen . A selenium-containing single-chain abzyme with potent antioxidant activity. Eur. J. Biochem . 2003, 270 (21): 4326-4331. (SCI, Impact factor 3.001)
14.Dan Su, Delin You, Xiaojun Ren, Guimin Luo , Ying Mu, Ganglin Yan, Yan Xue, Jiacong Shen, Kinetics Study of a Selenium-Containing ScFv Catalytic Antibody That Mimics Glutathione Peroxidase, Biochem. Biophys. Res. Commun ., 2001, 285(3): 702 - 707; (SCI, Impact factor 2.836)
15.Zhihua Jiang, Elias S.J. Arnér, Ying Mu , Linda Johansson, Jinming Shi, Siqi Zhao, Shujun Liu, Ruiying Wang, Tianzhu Zhang, Ganglin Yan, Junqiu Liu, Jiacong Shen and Guimin Luo , Expression of selenocysteine-containing glutathione S -transferase in Escherichia coli , Biochem. Biophys. Res. Commun. 321 ( 1 ): 94-101, 2004 (SCI, Impact factor 2.836)
16.Ye Sun, Ying Mu, Weijia Li, Shaowu Lv, Zhihua Jiang, K Zhang, Keyan Zheng, Feng Lin, Ganlin Yan, Guimin Luo, Junqiu Liu, Jiacong Shen, Protection of epidermal cells against UVB injury by the antioxidant selenium-containing single-chain Fv catalytic antibody. Arch. Biochem. Biophys . , 2003, 412 (1): 90-94. (SCI, Impact factor 2.338)
17.Xiaojun Ren, Liquan Yang, Junqiu Liu, Dan Su, Delin You, Chuanpen Liu, Kun Zhang, Guimin Luo , Ying Mu, Ganglin Yan, Jiacong Shen, A Novel Glutathione Peroxidase Mimic With Antioxidant Activity, Arch. Biochem. Biophys., 2001, 387(2): 250 - 256; (SCI, Impact factor 2.338)
18.Dan Su, Xiaojun Ren, Delin You, D. Li, Ying Mu, Ganglin Yan, Yan Zhang, Yuanming Luo, Yan Xue, Jiacong Shen, Zi Liu, Guimin Luo , Generation of three selenium-containing catalytic antibodies with high catalytic efficiency using a novel hapten design method, Arch. Biochem. Biophys., 2001, 395(2): 177 - 184; (SCI, Impact factor 2.338)
19.Ying Mu , Shaowu Lv , Xiaojun Ren , Guanghui Jin, Junqiu Liu , Ganlin Yan , Weijia Li, Jiacong Shen , Guimin Luo . UV-B induced keratinocyte apoptosis is blocked by 2-selenium-bridged beta-cyclodextrin, a GPX mimic. J Photoch photobio B, 2003, 69 (1): 7-12. (SCI, Impact factor 2.275)
20.Junqiu Liu, Kun Zhang, Xiaojun Ren , Guimin Luo , Jiacong Shen , Bioimprinted protein exhibits glutathione peroxidase activity , Analytica chimica acta, 504 (1): 185-189 , 2004 (SCI, Impact factor 2.210)
21.Jingyan Wei, Ying Mu, Diaqian Song, Xuexun,Fang X Liu, LS Bu, Hanqi Zhang, GZ Zhang, JH Ding, WZ Wang, QH Jin, GM Luo. A novel sandwich immunosensing method for measuring cardiac troponin I in sera. Anal Biochem, 2003, 321 (2): 209-216. (SCI, Impact factor 2.174)
22.X Liu, JY Wei, DQ Song, Z Zhang, H Zhang, GM Luo. Determination of affinities and antigenic epitopes of bovine cardiac troponin I (cTnI) with monoclonal antibodies by surface plasmon resonance biosensor. Anal Biochem, 2003, 314 (2): 301-309. (SCI, Impact factor 2.174)

实验室简介