文档介绍：摘要
摘要
含有非天然氨基酸的蛋白质(如翻译后修饰蛋白质、修饰有探针分子的蛋白质等)是化学生物学中重要的生理活性分子。这些分子难以通过生物表达来获取, 而必须使用化学方法来合成。半咣氨酸肽片段连接方法是目前应用于蛋白质化学全合成中的一种重要方法,该方法能够在温和的水溶液中高效地实现肽片段的连接,从而生成天然或者非天然的蛋白质。这种连接方法要求多肽的N端必须是半胱氨酸,%。此外,这种肽片段连接方法还要求参与偶联的另一段肽其C端必须是肽硫酯,但肽硫酯在溶液中稳定性较差, 且不易用常规的Fmoc固相合成方法制备得到。因此,如何改进这种方法使其能够摆脱半胱氨酸和硫酯的限制,对于蛋白质的全合成具有极为重要的价值。
在本论文中作者发展了在肽链N端第一个酰胺氮原子上使用可脱去的巯基修饰基团的远程肽片段连接方法,实现J,多肽C端硫酯与N端多种类型氨基酸在温和条件下的连接反应,扩充了连接位点的多样性,从而摆脱了传统半胱氨酸肽片段连接方法对N端半胱氨酸的限制以及在肽链N端氨基上使用易脱去的巯基修饰基团的方法对甘氨酸的限制。
关键词:肽片段连接半胱氨酸硫酯远程肽片断连接巯基修饰基团
Abstract
Abstract
Proteins that contain amino acid residues fsuch as modified proteins and proteins functionalized with synthetic probes)are highly important molecules in chemical molecules can’t be readily obtained through biological expression,SO that the only approach to produce them is to use chemical the most important method in the field of chemical synthesis of protein iS native chemical can ef葡ciently condense peptide segments in aqueous solutions under mild conditions to generate
natural as well as ,there are some limitations in this
,a cysteine residue iS needed at the ligation site while the abundance of cysteine in proteins iS only %. other part involved in the native chemical ligation must be a iS usually unstable in solution and can not be prepared mom Fmoc-,developing new methods to break through the above limitations could be valuable for the total synthesis of
proteins.
In this paper,we developed a new remote peptide ligation method to e cysteine limitations of ligation synthesized a series pounds with difrerent sulfur-displaying auxiliaries on the nitrogen of the Iast amide and conducted their ligation with thioesters under mild conditions ,the
ligation residues which are applicable in native chemical ligation are no longer limited