多肽与朊蛋白相互作用研究  

Interaction study of peptides and prion protein

作　　者：胡萍萍[1] 甄淑君 陈礼强[1] 黄承志 

机构地区：[1]发光与实时分析教育部重点实验室,西南大学生命科学学院,西南大学药学院,西南大学化学化工学院,重庆400715

出　　处：《中国科学：化学》2010年第6期733-738,共6页SCIENTIA SINICA Chimica

基　　金：国家重大科学基础研究计划(2006CB933100)基金资助

摘　　要：朊病毒病是一类累及多种动物和人类中枢神经系统退行性疾病,但至今针对这类疾病尚无有效的治疗方法.考虑到在180位的缬氨酸突变为异亮氨酸的180I突变蛋白的突变位点与朊蛋白181位的糖基化位点非常接近,其生物化学性质对朊病毒病的影响非常重要.本文针对180I突变蛋白的182-190段序列设计了KNFTK、KTDVE、EMMKE和EVVKK等四种αxyzβ型多肽.研究发现,四种多肽中只有EVVKK能稳定蛋白的构象,同时诱导β-折叠向α-螺旋的转变,而其他三种蛋白对180I的结构基本没有影响.该结论对于开发多肽药物并进一步用于临床治疗具有一定的借鉴作用.Prion diseases are a class of central nervous system degenerative diseases involving a variety of animal and human beings.Presently,prion diseases have taken place in many countries in the world,which possess a great threat to human health.However,there is no effective treatment against these diseases.Previous investigations showed that the sequence-related peptides play an important role in stabilizing the conformation of prion protein.We performed a biochemical study of the 180I point mutation（a valine to isoleucine mutation） in this communication.As this mutation is near the glycosylation site at position 181,it plays an important role in the pathological prion disease.In this report,we designed four αxyzβ type peptides for sequence range of 182-190 of 180I.The results showed that only the sequence of EVVKK can bring a very good stability,and induce the conformation changes from β-sheet to α-helix,while the effect of other three peptides can be neglected,which can act as a reference for the development of peptide drugs,and further for the clinical treatment.

关 键 词：朊病毒病 朊蛋白 突变 多肽 圆二色 

分 类 号：R742.9[医药卫生—神经病学与精神病学]