N端结构改造的抑咽侧体素拟肽类化合物的设计、合成及生物活性研究  

Design,synthesis and biological activity of peptidomimetic analogs with allatostatin at N-terminus

作　　者：汪梅子[1] 王献伟[1] 吴小庆[1] 李欣潞[1] 杨新玲[1] 

机构地区：[1]中国农业大学理学院应用化学系,北京100193

出　　处：《中国科学：化学》2016年第11期1235-1241,共7页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:21372257)资助项目

摘　　要：抑咽侧体素（Allatostatin,AST）是一类具有抑制咽侧体合成保幼激素（JH）功能的昆虫神经肽.然而,由于天然AST易代谢失活,限制了其在害虫控制方面的应用.本研究在前期工作基础上,以高活性拟肽类化合物B1作为二级先导,采用模拟肽学方法进行结构改造,通过N端引入脲桥结构消除酶解位点,以提高抗酶解能力,共设计合成了10个目标化合物II01~II10,并对其抑制保幼激素合成离体生物活性进行了测定.结果表明,10个化合物均具有抑制保幼激素合成活性,其中,II04（IC_（50）=0.21μmol/L）抑制活性略高于一级先导天然核心五肽（IC_（50）=0.24μmol/L）.虽然抑制活性比二级先导B1（IC_（50）=0.09μmol/L）略低,但简便的合成路线,使其成为具有研究潜力的先导化合物.Allatostatins（ASTs） comprise a family of insect neuropeptides that inhibit juvenile hormone（JH） biosynthesis. However, their susceptibility to both exo- and endopeptidases precludes their application in pest control. In our previous studies, a peptidomimetic analog B1 with high ability to inhibit JH biosynthesis（IC_（50）=0.09 μmol/L） was discovered, which was more active than the lead core pentapeptide（IC_（50）=0.24 μmol/L） by the corpora allata（CA） of the cockroach Diploptera punctata in vitro. In this work, based on lead B1, a series of ASTs analogs with different aromatic group at N-terminus were designed by introducing urea linkage to protect peptidase-susceptible sites. The bioactivity indicated that all analogs showed good inhibition on juvenile hormone（JH） biosynthesis. The activity of analog II04（IC_（50）=0.209 μmol/L） was slightly higher than that of the core pentapeptide. Although the value is lower than B1, the simpler synthesis route than B1, makes it the potential to be used as a new lead compound.

关 键 词：抑咽侧体素 模拟肽学 拟肽类化合物 保幼激素生物合成 

分 类 号：O629.72[理学—有机化学]