在3月23日召开的上海市科学技术大会上，生化与细胞所戚正武院士领衔的“活性多肽毒素结构与功能的研究”荣获上海市科学技术进步一等奖。
该项目从东亚马氏钳蝎及我国南海各种芋螺中获得多种新的神经毒素，并深入研究了它们的蛋白质与基因结构、生理功能及其构效关系。
在对东亚马氏钳蝎神经毒素的研究中，研究者阐明了钠通道毒素B－mKM1的蛋白与基因结构，利用蛋白质工程获得15个突变体，深入研究其构效关系。发现新的钾通道毒素，具有高度选择性。发现具有双功能的BmTx3，既可阻断A型钾电流，也可抑制HERG钾通道。提出毒素阻断离子通道的新机理。阐明了全蝎作为重要抗癫痫及镇痛的物质基础。
在芋螺毒素研究方面，研究者从桶形芋螺中纯化并克隆了■－BtX，它代表芋螺毒素中一新的超家族，是首次报道的钾通道开放剂。从线纹芋螺中克隆了μ－SIIIA，可作为先导化合物用于新的镇痛药物的开发。从多种芋螺中纯化及克隆了M超家族中新一类芋螺毒素，提出了芋螺毒素超家族分类的新原则。从6种芋螺中纯化、鉴定了新的多肽毒素40个左右，克隆鉴定的新基因超过60个，涵盖了各种超家族。
该成果共发表SCI论文27篇，被他人引用197次，论文总影响因子为94.4，单篇最高影响因子为13.3。该成果不仅对神经学科的研究，而且对开发治疗多种神经性疾病的新药具有重要意义。
戚正武院士简介
生物化学家。1932年4月出生于宁波。1952年毕业于同济大学化学系，
1959年获苏联莫斯科医学科学院生物与医学研究所副博士学位。
1981-1982年以及1987年、1995年分别于美国Purdue 及Notre Dame大学进行学术交流。曾担任数届国际《血栓研究》杂志的编委，现任《中国科学》,《生物化学与生物物理学报》及其他国内多种学术期刊的编委。现兼同济大学蛋白质研究所所长及化学系主任。
1999年被评为中国科学院院士，
2001年被评为第三世界科学院院士。
长期从事蛋白质，活性多肽，尤其是蛋白酶及其抑制剂的研究。其中慈菇蛋白酶抑制剂为国内首先发现的新的抑制剂家族，有明显的中国特色，还克隆了凝血因子FVIII及vWF的全cDNA基因，并在CHO和BHK细胞中进行了表达。近年来又解析了中华马氏钳蝎毒素中多种Na+通道毒素的氨基酸序列及其基因结构，通过基因突变研究其结构与功能的关系，并开展了其它K+,Ca++及Cl-通道神经毒素的研究，近来又找到了新的神经毒素，从而开辟了新的研究领域。
发表论文百余篇，大多数刊登在国外主要学术期刊及英文版"中国科学"上，培养博士生及硕士生各20名。曾获得中国科学院自然科学奖二等奖3次，一等奖1次，获国家自然科学奖三等奖2次，1981年慕尼黑国际激肽会议上获优秀论文奖。
长期以来从事活性多肽及酶蛋白结构与功能的研究，利用蛋白质工程技术研究结构与功能的关系。有关蛋白酶抑制剂，蝎及芋螺多肽神经毒素以及与凝血纤溶有关的蛋白质的研究居国际前沿。曾从不同植物中分离纯化了三种不同类型的蛋白酶抑制剂，阐明了它们的蛋白质、基因及晶体结构，确定了活性中心位置，其中多功能双头慈菇蛋白酶抑制剂是属于新的抑制剂家族。利用多肽合成，蛋白酶限止性降解及蛋白质工程等手段研究了它们的结构与功能的关系。在基因水平上阐明了异常人血清白蛋白及血小板无力症遗传性疾病的基因缺陷。对凝血因子Ⅷ及vWF因子进行了基因克隆，并在哺乳动物细胞中获得表达，申请了生产重组凝血因子Ⅷ的专利。90年代以来又开展研究蝎及芋螺毒腺中各种离子通道及神经递质受体的神经毒素,发现了多种结构全新的神经毒素。此外在猪肝中分离纯化了与体内重要生理功能相关的天然蛋白质前体加工酶的抑制剂。
典型论文列表:
1. Hui-ling Yang, Rong-shu Luo, Li-xiu Wang, De-xu Zhu and Cheng-wu Chi Primary Structure and Disulfide Bridge Location of Arrowhead Double-headed Proteinase Inhibitors. J. Biochem. (Tokyo) 111, 537, 1992.
2. Xiao-ming Chen, Yue-wei Qian, Ke-da Gan and Cheng-wu Chi Chemical Synthesis, Molecular Cloning, and Expression of the Gene Coding for the Trichosanthes Trypsin Inhibitor -a Squash family Inhibitor. J. Biochem. (Tokyo) 112, 45, 1992.
3. Wen-feng Xu, Wei-kang Tao, Zhen-zhen Gong and Cheng-wu Chi cDNA and Genomic Structures of Arrowhead Proteinase Inhibitors J. Biochem. (Tokyo) 113, 153, 1993.
4. Min-hua Ling, Hai-yan Qi and Cheng-wu Chi Protein, cDNA, and Genomic DNA Sequences of the Towel Gourd Trypsin Inhibitor -- a Squash Family Inhibitor. J. Biol. Chem. (US) 268, 810, 1993.
5. Wei-chang Zan, Wen-feng Xu and Cheng-wu Chi Protein and Gene Structure Analysis of an Albumin Genetic Variant: Proalbumin Wu Yang (-2 Arg--His). Int. J. Peptide Protein Res. 41, 441, 1993.
6. Jian-ming Gu, Wen-feng Xu, Xiao-dong Wang, Cheng-wu Chi and Chang-geng Ruan Identification of a Nonsense Mutation at Amino Acid 584-Arg of Platelet Glycoprotein Iib in Patients with TypeI Glanzmann Thrombasthenia. British J. Hematology 83, 442, 1993.
7. Ling Wang, Xiao-hong Lin, Da-fu Cui, Zhen-yi Wang and Cheng-wu Chi★ Assignment of the Binding Site for Tissue Plasminogen Activator on Human Fibronectin J. Biol. Chem. (US) 269, 4332,1993.
8. Guang-da Lin, Wolfram Bode, Robert Huber, Cheng-wu Chi and Richard A. Engn The 0.25 nm X-ray Structure of the Bowman-Birk Type Inhibitor from Mung Bean in Ternary Complex with Porcine Trypsin. Eur. J. Biochem. 212, 549, 1993.
9. Yi-li Li, Qi-chen Huang, Shi-wei Zhang, Cheng-wu Chi and You-qi Tang Studies on anArtificial Trypsin Inhibitor Peptide Derived from the Mung Bean Trypsin Inhibitor: Chemical Synthesis, Refolding, and Crystallographic Analysis of its Complex with Trypsin. J. Biochem. (Tokyo) 116, 18, 1994.
10. Zhi-wei Xie, Ming-juan Luo, Wen-feng Xu and Cheng-wu Chi Two Reactive Site Location and Structure-Function Study of the Arrowhead Protease Inhibitors,A and B, Using Mutagenesis. Biochemistry (US) 36, 5846, 1997.
11. Ming-juan Luo, Wu-yuan Lu and Cheng-wu Chi Clarification of an Uncertain Intron within the cDNA Sequences of Arrowhead Proteinase Inhibitor A and B. J. Biochem. (Tokyo) 121, 991, 1997.
12. Ming-juan Luo, Yu-mei Xiong, Miao Wang, Da-cheng Wang and Cheng-wu Chi Purification and Sequence Determination of a New Neutral Mammalian Neurotoxin from Scorpion Buthus martensii Karsch. Toxicon 35, 723, 1997.
13. Yu-mei Xiong, Min-hua Ling, Da-cheng Wang and Cheng-wu Chi The cDNA and Genomic DNA Sequences of a Mammalian Neurotoxin from the Scorpion Buthus martensii Karsch. Toxicon 35, 1025, 1997.
14. Yu-mei Xiong, Min-hua Ling, Zheng-dao Lan, Da-cheng Wang and Cheng-wu Chi The cDNA Sequence of an Excitatory Insect Selective Neurotoxin from the Scorpion Buthus martinsi Karsch. Toxicon 37, 335, 1999.
15. Zheng-dao Lan, Li Dai, Xiao-liang Zhuo, Ke Xu, Jun-Cai Feng and Cheng-wu Chi Gene Cloning and Sequencing of BmK AS and BmK As-1, Two Novel Neurotoxins from the Scorpion Buthus martinsi Karsch. Toxicon 37, 815, 1999.
16. Yu-mei Xiong, Zheng-dao Lan, Miao Wang. Bo Liu, Xin-qi Liu, Hao Fei, Lai-gen Xu, Qi-Chang Xia, Chung-guang Wang, Da-cheng Wang and Cheng-wu Chi Molecular Characterization of a New Excitatory Insect Neurotoxin with an Analgesic Effect on Mice from the Scorpion Buthus martinsi Karsch. Toxicon 37, 1165, 1999.
17. Jing-jiang Wu, Li Dai, Zheng-dao Lan and Cheng-wu Chi Genomic Organization of Three Neurotoxins Active on Small Conductance Ca++-activated Potassium Channels from the Scorpion Buthus martinsi Karsch. FEBS Letters 452, 360, 1999.
18. Chun Chen, Xiao-dong Fang, Jiang Zhu, Xiang-fu Wu, Zu-chuan Zhang, Zheng-yi Wang and Cheng-wu Chi The Gene Expression of Coagulation Factor VIII in Mammalian Cell Lines. Thrombosis Res. 95, 105, 1999.
19. Yan-shi Zhu, Qi-chen Huang and Cheng-wu Chi Crystal Structure of Mung Bean Inhibitor Lysine Active Fragment Complex with Bovine ?-trypsin at 1.8 ? Resolution. J. Biomolecular Structure and Dynamics 16, 1219, 1999.
20. Feng Shao, Yu-mei Xiong, Rong-huan Zhu, Min-hua Ling, Cheng-wu Chi & Da-cheng Wang Expression and Purification of the BmK M1 Neurotoxin from the Buthus martinsi Karsch. Protein Expression and Purification 17, 358, 1999.
21. Jing-jiang Wu, Li Dai, Zheng-dao Lan and Cheng-wu Chi The Gene Cloning and Sequencing of Bm-12, a Chlorotoxin-like Peptide from the Scorpion Buthus martinsi Karsch. Toxicon 38, 661, 2000.
22. Li Dai, Jing-jiang Wu, Yi-hua Gu, Zheng-dao Lan, Min-hua Ling and Cheng-wu Chi Genomic organization of three novel toxins from the scorpion Buthus martinsi Karsch that are active on potassium channels. Biochem. J. 346, 805, 2000.
23. Hao Fei, Yan LI, Li-Xiu Wang, Ming-Juan Luo, Min-Hua Ling, Cheng-Wu Chi Purified nonhistone protein from porcine kidney acts as a suicide substrate inhibitor on furin-like enzyme. Acta Pharmacol. Sin. 21, 265, 2000.
24. Xiang-Dong Fang, Chun Chen, Qi Wang, Jian-Xin Gu, Cheng-Wu Chi The Interaction of the Calcium and Integrin Binding Protein (CIBP) with the Coagulation Factor VIII Thromb. Res. 102, 177, 2001.
25. Chun-Guang Wang, Xiao-Lin He, Feng Shao, Wei Liu, Min-Hua Ling, Da-Cheng Wang, Cheng-Wu Chi Molecular characterization of an anti-epilepsy peptide from the scorpio Buthus martensi Karsch. Eur. J. Biochem. 268, 2480, 2001.
26. Guang-yu Zhu, Qi-chen Huang, Yan-shi Zhu, Cheng-wu Chi, You-qi Tang X-ray study on an artificial mung bean inhibitor complex with bovine ?-trypsin in neat cyclohexane. Biochim. Biophys. Acta 1546, 98, 2001.
27. Chun Chen, Qi Wang, Xiang-dong Fang, Qin Xu, Cheng-wu Chi and Jian-xin Gu Roles of the phytanoyl CoA ?-hydroxylase in mediating the expression of human coagulation factor VIII. J. Biol. Chem. 276, 46340, 2001.
28. Jing-Jiang Wu, Lin-Lin He, Zhuan Zhou and Cheng-Wu Chi Gene expression, mutation and structure-function relationship of scorpion toxin BmP05 active on SKCa channels.Biochemistry 41, 2844, 2002.
29. Jiong Li, Cheng-wu Chi, Kang-cheng Ruan Conformation nearby Trp residues of APIA and APIB modulates the inhibitory specificity of the protease. Acta Biochi. Biophys. Sinica 34, 494, 2002.
30. Jiong Li, Kang-cheng Ruan, Cheng-wu Chi The assignment of the reactive sites of the double-headed arrowhead proteinase inhibitor A and B. Acta Biochi. Biophys. Sinica 34, 662, 2002.
31. C. Goudet, Cheng-wu Chi, J.Tytgat An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch. Toxicon. 40(9), 1239, 2002
32. Wang CG, Stankiewicz M, Ling MH, Pelhate M, Wang DC and Chi CW★. Purification of two depressant insect neurotoxins and their gene cloning from the scorpion Buthus martensi Karsch. J. Pept. Res. 61(1): 7-16, 2003.
33. Wang CG, Gilles N, Hamon A, Le Gall F, Stankiewicz M, Pelhate M, Xiong YM, Wang DC and Chi CW Exploration of the functional site of a scorpion alpha-like toxin by site-directed mutagenesis. Biochemistry 42 (16), 4699-4708, 2003
34. Fan CX, Chen XK, Zhang C, Wang LX, Duan KL, He LL, Cao Y, Liu SY, Zhong MN, Ulens C, Tytgat J, Chen JS, Chi CW, and Zhou Z. A novel conotoxin from conus betulinus, k-BtX, unique in cysteine pattern and in function as a specific BK channel modulator.J Biol Chem. 278(15), 12624-12633, 2003
35. Chen-Qi Xu, Shun-Yi Zhu, Cheng-Wu Chi and Jan Tytgat Turret and pore block of K+Channels: what is the different? Trends Pharmac. Sci. 24(9): 446-449, 2003
