刘俊秋
人工酶的分子设计和生物超分子方向的研究工作
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- 姓名:刘俊秋
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学术头衔:
博士生导师, 教育部“新世纪优秀人才支持计划”入选者
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学科领域:
高分子化学
- 研究兴趣:人工酶的分子设计和生物超分子方向的研究工作
刘俊秋教授,男,1965年1月生。1989年毕业于吉林大学化学系,获学士学位,1990年和1999年于吉林大学化学系高分子化学与物理专业分别获理学硕士和博士学位。近年来,在主要从事人工酶的分子设计和生物超分子方向的研究工作。主持或参加了多项国家863、973、自然基金等研究项目。2002.1-2003.9作为洪堡学者在德国从事博士后研究,开展了分子印迹模拟酶的研究工作。2004年入选国家教委新世纪优秀人才培养计划。近年来,在国内外发表学术论文60余篇,在国际权威杂志如Angew.Chem. Int. Ed.; J.Am. Chem.Soc。;Chemistry & Biology和 J Biol Chem等权威杂志发表了一批学术论文,特邀编写? Handbook of Food Enzymology?。
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【期刊论文】Highly Efficient Dendrimer-Based Mimic of Glutathione Peroxidase
刘俊秋, Xi Zhang, *, † Huaping Xu, †, ‡ Zeyuan Dong, ‡ Yapei Wang, † Junqiu Liu, ‡ and Jiacong Shen‡
J. AM. CHEM. SOC. 9 VOL. 126, NO.34, 2004,-0001,():
-1年11月30日
In this communication, we report the synthesis of the three generations of Fre
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【期刊论文】Bioimprinted protein exhibits glutathione peroxidase activity
刘俊秋, Junqiu Liu a, * Kun Zhang b, Xiaojun Ren a, Guimin Luo b, Jiacong Shen a
Analytica Chimica Acta 504(2004)185-189,-0001,():
-1年11月30日
A strategy for design of bioimprinted proteins with glutathione peroxidase (GPX) activity has been proposed. The proteins imprinted with a glutathione derivative were converted into selenium-containing proteins by chemical modifying the reactive hydroxyl groups of serines followed by sodium hydrogen selenide displacement. These selenium-containing proteins exhibited remarkable GPX activities and the GPX activities of reduction of H2O2 by glutathione (GSH) were found to be 101-817U mol−1, which approaches the activity of a selenium-containing catalytic antibody elicited by a hapten similar to our template. The steady state kinetic study for imprinted protein catalysis revealed Michaelis–Menten kinetics for both H2O2 and GSH, e.g. the pesudo-first-order rate constant kcat (H2O2) and the apparent Michaelis constant Km (H2O2) at 1mM GSH were calculated to be 784min−1 and 1.24×10−3 M, respectively, and the apparent second-order rate constant kcat (H2O2)/Km (H2O2) was determined to be 6.33×105 (M min)−1. The kinetics and the template inhibition showed that the strategy might be a remarkably efficient one for generating artificial enzyme with GPX activity.
Bioimprining, Glutathione peroxidase, Protein, Catalysis, Selenium
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【期刊论文】A Novel Cyclodextrin-Derived Tellurium Compound with Glutathione Peroxidase Activety
刘俊秋, Xiaojun Ren, [a, b] Yan Xue, [a] Junqiu Liu, [b] Kun Zhang, [a] Jian Zheng, [c] Guimin Luo, *[a] Canhui Guo, [a] Ying Mu, [a] and Jiang Shen[b, c]
ChemBioChem 2002.3, 356-363,-0001,():
-1年11月30日
A novel dicyclodextriyl ditelluride (2-TeCD) compound was devised as a functional mimic of the glutathione peroxides (GPX) enzymes that nomally remove hydroperoxides from the cell. The GPX activity of the mimic was found to be 46.7U
Artificial enzymes
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刘俊秋, Xiaojun Ren, , Per Jemth, Philip G. Board, Guimin Luo, Bengt Mannervik, Junqiu Liu, Kun Zhang, and Jiacong Shen
Chemistry & Biology, Vol. 9, 789-794, July, 2002,-0001,():
-1年11月30日
Glutathione peroxidase (GPX) protects cells against oxidative damage by catalyzing the reduction of hydro-peroxides by glutathione (GSH). GPX therefore has potential therapeutic value as an antioxidant, but its pharmacological development has been limited be-cause GPX uses a selenocysteine as its catalytic group and it is difficult to generate selenium-containing pro-teins with traditional recombinant DNA technology. Here, we show that naturally occurring proteins can be modified to generate GPX activity. The rat theta-thiclass glutathione transferase T2-2 (rGST T2-2) pre-sents an ideal scaffold for the design of a novel GPX catalyst because it already binds GSH and contains a natuserine close to the substrate binding site, which can engibe chemically modified to bind selenium. The modified Se-rGST T2-2 efficiently catalyzes the reduction of hy-drogen peroxide, and the GPX activity surpasses the activities of some natural GPXs.
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刘俊秋, Jun-qiu Liu and Gnter Wulff*
Angew. Chem. Int. Ed. 2004, 43, 1287-1287,-0001,():
-1年11月30日
Mimicking of natural enzyme systems with catalytically active arrangements in designed receptors is a challenging topic for chemists. Notable achievements to date have been obtained with several model systems, such as synthetic macrocyclic compounds, molecular assemblies, catalytic antibodies, and molecularly imprinted polymers.[1] Among these models, molecular imprinting has been demonstrated to be an attractive strategy for creating catalytically active binding sites for enzyme mimetics.[2] This method should give the opportunity to generate more complicated active sites with a high similarity to natural systems. For this purpose, to mimic enzyme behavior, especially esterase activity, numerous experiments have been undertaken by imprinting with transition-state analogues (TSAs).[3, 4] Although the earlier attempts to mimic enzyme behavior using imprinted polymers showed only limited catalytic efficiency, significant rate enhancement by catalysis with imprinted polymers has been obtained in recent years.[4] Evidently, increasing the transition-state binding, as well as correctly incorporating and positioning the functional groups is essential for the construction of an effective enzyme model.[1–4] In our previous work on preparing polymer catalysts by molecular imprinting,[4] amidinium functional groups were oriented in imprinted cavities. These groups acted as anchors for binding the tetrahedral transition states of basic ester or carbonate hydrolysis in a similar manner to the catalytic role of guanidinium moieties in certain catalytic antibodies [1c] and in carboxypeptidase A.[5] The catalytic action of carboxypeptidase Ainvolves two guanidinium groups and a Zn2+ ion. The guanidinium moiety of Arg127 binds the oxyanion generated in the rate-limiting formation of the tetrahedral transition
enzyme models
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刘俊秋, Hui-jun Yu‡, Jun-qiu Liu‡§, August Bo˝ck¶, Jing Li‡, Gui-min Luo, and Jia-cong Shen‡
Vol. 280, No.12, Issue of March 25, pp. 11930-11935, 2005,-0001,():
-1年11月30日
Glutathione peroxidase (GPx, EC 1.11.1.9) protects cells against oxidative damage by catalyzing the reduction of hydroperoxides with glutathione (GSH). Several attempts have been made to imitate its function for mechanical study and for its pharmacological development as an antioxidant. By replacing the active site serine 9 with a cysteine and then substituting it with selenocysteine in a cysteine auxotrophic system, catalytically essential residue selenocysteine was bioincorporated into GSH-specific binding scaffold, and thus, glutathione Stransferase (GST, EC 2.5.1.18) from Lucilia cuprina was converted into a selenium-containing enzyme, seleno-LuGST1-1, by genetic engineering. Taking advantage of the important structure similarities between seleno-LuGST1-1 and naturally occurring GPx in the specific GSH binding sites and the geometric conformation for the active selenocysteine in their common GSH binding domain-adopted thioredoxin fold, the as-generated selenoenzyme displayed a significantly high efficiency for catalyzing the reduction of hydrogen peroxide by glutathione, being comparable with those of natural GPxs. The catalytic behaviors of this engineered selenoenzyme were found to be similar to those of naturally occurring GPx. It exhibited pH and temperaturedependent catalytic activity and a typical ping-pong kinetic mechanism. Engineering GST into an efficient GPx-like biocatalyst provided new proof for the previous assumption that both GPx and GST were evolved from a common thioredoxin-like ancestor to accommodate different functions throughout evolution.
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【期刊论文】A bis-cyclodextrin diselenide with glutathione peroxidase-like activity
刘俊秋, Jun-qiu Liu a, b, Gui-min Luo a;*, Xiao-jun Ren c, Ying Mu a, Yan Bai b, Jia-cong Shen c
Biochimica et Biophysica Acta 1481(2000)222-228,-0001,():
-1年11月30日
A diselenide, 2, 2P-diseleno-bis-L-cyclodextrin (2-SeCD), was synthesized to imitate the antioxidant enzyme glutathione peroxidase (GPX). The GPX mimic accepts a variety of hydroperoxides as substrates. The GPX activities, reduction of H2O2, tert-butyl hydroperoxide and cumenyl hydroperoxide by glutathione, are 7.4, 4.5 and 10.2 U/Wmol, respectively. In contrast to ebselen (PZ51), the diselenide displays high GPX-like activity. The reduction of hydroperoxide by glutathione in the presence of a radical trap shows that the mimic catalyzes the reaction via a non-radical mechanism. A ping-pong mechanism was observed in the steady-state kinetic studies of the 2-SeCD-catalyzed reaction.
L-Cyclodextrin, Glutathione peroxidase, Imitating enzyme, Selenium
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刘俊秋
,-0001,():
-1年11月30日
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刘俊秋, Zeyuan Dong, Junqiu Liu, * Shizhong Mao, Xin Huang, Bing Yang, Xiaojun Ren, Guimin Luo, and Jiacong Shen
J. AM. CHEM. SOC. 9 VOL. 126, NO.50, 2004,-0001,():
-1年11月30日
Artificial glutathione peroxidase (GPx) model 2, 2'-ditellurobis(2-deoxy-,-cyclodextrin) (2-TeCD) which has the desirable properties exhibited high substrate specificity and remarkably catalytic efficiency when 3-carboxy-4-nitrobenzenethiol (ArSH) was used as a preferential thiol substrate. The complexation of ArSH with,-cyclodextrin was investigated through UV spectral titrations, fluorescence spectroscopy, 1H NMR and molecular simulation, and these results indicated that ArSH fits well to the size of the cavity of,-cyclodextrin. Furthermore, 2-TeCD was found to catalyze the reduction of cumene peroxide (CuOOH) by ArSH 200 000-fold more efficiently than diphenyl diselenide (PhSeSePh). Its steady-state kinetics was studied and the second rate constant kmax/ KArSH was found to be 1.05 107 M-1 min-1 and similar to that of natural GPx. Moreover, the kinetic data revealed that the catalytic efficiency of 2-TeCD depended strongly upon the competitive recognition of both substrates for 2-TeCD. The catalytic mechanism of 2-TeCD catalysis agreed well with a ping-pong mechanism, in analogy with natural GPx, and might exert its thiol peroxidase activity via tellurol, tellurenic acid, and tellurosulfide.
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刘俊秋, Jun-qiu Liu† and Günter Wulff*, ‡
J. AM. CHEM. SOC. 9 VOL. 126, NO.24, 2004 ,-0001,():
-1年11月30日
Designing efficient artificial mimics for naturally occurring enzymes has been a challenging area to chemists and biologists. 1 Inspired by the concept of transition-state stabilization in enzyme catalysis, 2 catalytically quite active antibodies have been raised against stable transition-state analogues (TSAs) of the corresponding reaction. 3 Similarly, molecularly imprinted polymers 4 offer an excellent possibility to mimic the active site of natural enzymes since not only can the shape of the transition state be mimicked by imprinting but also at the same time suitable catalytic groups and binding sites can be introduced into the active site in a predetermined orientation. 5-7 However, only recently has strong catalytic activity approaching6e or surpassing7 the activity of the catalytic antibodies been reported.
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