法尼基转移酶抑制剂——CAAX四肽类似物  

CAAX tetrapeptide analogs:farnesyltransferase inhibitors

作　　者：王哲理[1] 闫磊[1] 兰文军[1] 

机构地区：[1]山东轻工业学院生物医学工程研究所,山东济南250353

出　　处：《中国新药与临床杂志》2013年第8期608-613,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金面上项目(81171413);山东省博士基金(BS2010YY044);济南市中小企业创新基金(2010007)

摘　　要：法尼基转移酶抑制剂(FTIs)是一类以细胞信号转导分子Ras蛋白的修饰酶——法尼基(异戊二烯)转移酶(FTase)为药靶的抗肿瘤先导物。FTase催化Ras蛋白的法尼基化修饰,疏水性的法尼基可引导法尼基化Ras蛋白靶向定位于含有疏水基团的细胞膜而介导细胞信号传导。若变异Ras蛋白持续处于活化状态,细胞信号传导紊乱,可致细胞持续增生而发生肿瘤。通过抑制FTase活性、阻断Ras蛋白靶向定位,FTIs能够有效抑制肿瘤细胞增殖。目前许多人工合成寡肽类似物被设计为FTIs,本文综述了基于CAAX四肽类似物的FTIs研究进展。Farnesyhransferase inhibitors （FTIs） target farnesyltransferase （FTase） catalyzing the post protein. Hydrophobic farnesyl localizes farnesylated have been defined as anti-carcinoma precursors, which translational farnesylation of a signaling molecule Ras -Ras protein within cellular membrane consisting of hydrophobic groups, thereby Ras protein mediates signalling transduction. Mutant Ras protein leads to cellular signal transduction dysfunctions and results in carcinoma. FTIs can effectively inhibit cancer cell proliferation by attenuating FTase activity and blocking Ras protein localization. Many artifical synthesis oligopeptides or analogs have been designed as FTIs. The development of CAAX tetrapeptide analogs- based FTIs is reviewed in this paper.

关 键 词：抗肿瘤药 药物疗法 Ras蛋白质类 法尼基转移酶抑制剂 法尼基转移酶 CAAX 

分 类 号：R979.1[医药卫生—药品]