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抗c—erbB—2 ribozyme的计算机设计
引用本文:毕锋,张学庸.抗c—erbB—2 ribozyme的计算机设计[J].第四军医大学学报,1997,18(1):6.
作者姓名:毕锋  张学庸
作者单位:第四军医大学西京医院全军消化疾病研究所!西安710033(毕锋,张学庸,樊代明),第四军医大学生物化学及分子生物学教研室(惠宏襄,王成济)
基金项目:国家自然科学基金资助课题No.39500066
摘    要:设计能特异性切割人癌基因c-erbB-2mRNA的核酶。概据Symonx的“猛士锤头结构”,以人癌基因c-erbB-2mRNA为靶RNA,用计算机对其可能为核酶切割的位点进行分析以寻找最佳切点。对底物及核酶的二级结构进行预测。

关 键 词:c-erbB-2  ribozyme  计算机设计  基因疗法  肿瘤

Computer design of anti-c-erbB-2 ribozymes
Bi Feng,Zhang Xueyang,Fan Daiming,Hut Hangxiang,Wang ChengjiInstitute of Digestive Disease of PLA,Fourth Military Medical University,Xi'an.Computer design of anti-c-erbB-2 ribozymes[J].Journal of the Fourth Military Medical University,1997,18(1):6.
Authors:Bi Feng  Zhang Xueyang  Fan Daiming  Hut Hangxiang  Wang ChengjiInstitute of Digestive Disease of PLA  Fourth Military Medical University  Xi'an
Institution:Bi Feng,Zhang Xueyang,Fan Daiming,Hut Hangxiang,Wang ChengjiInstitute of Digestive Disease of PLA,Fourth Military Medical University,Xi'an 710033 Department of Biochemistry and Molecular Biology,Fourth Military Medical University
Abstract:Objective:To design the ribozymes which may cleave the mRNA of human c-erbB-2 oncogene. Methods: The c-erbB-2 mRNA was taken as the target RNA. Ribozymes were designed according to the "hammerhead structure" described by Symons. Computer was used to analyze the possible secondary cleavage sites on c-erbB-2 mRNA and to predict the secondary structures of substrate and ribozymes. Results: The secondary structures of c-erbB-2 mRNA from nt 2428 to nt 2776 and nt 2820 to nt 3004 were relatively stable. The two regions were of important biological function and were the ideal attacking regions for ribozymes. Three ribozymes targeting the nt 2438, nt 2477 and nt 2751 on the c-erbB-2 mRNA were designed and were named RZ1, RZ2 and RZ3 respectively. The hammerhead structures composed of ribozymes and targeting mRNA could be formed by computer imitation. No analogous sequence of substrate which combined with ribozyme was found in the mRNA of other genes in known human Gen Bank through computer probe. Conclusion: Not all GUX or CUX could be taken as the cleavage site of ribozyme. The nt 2438, nt 2477 and nt 2751 on the c-erbB-2 mRNA are the most ideal attacking sites for ribozymes.
Keywords:c-erbB-2 ribozyme computer design
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