Synthesis and biological evaluation of the geometric farnesylated analogues of the a-factor mating peptide of Saccharomyces cerevisiae.
Synthesis and biological evaluation of the geometric farnesylated analogues of the a-factor mating peptide of Saccharomyces cerevisiae.
复制标题
酿酒酵母α因子交配肽的几何法尼基化类似物的合成和生物学评价。
DOI：
10.1021/jo000942m
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Gibbs,RA
中科院分区：
文献类型：
--
作者：
Xie,H;Shao,Y;Becker,JM;Naider,F;Gibbs,RA
酿酒酵母的茶因子是一种十二肽信息素（YIIKGVFWDPAC（法尼基）- och3,1），其翻译后修饰需要法尼基类异戊二烯和羧甲基才能获得充分的生物活性。该肽已被用作一个模型系统来探索法尼酰半胱氨酸片段的生物学功能，这是许多关键哺乳动物蛋白质的生物活性所必需的。本研究的目的是确定天然e -法尼基部分的双键异构化对茶因子生物活性的生物学效应。一个统一的，立体选择性合成路线的三个几何异构体e， e -法尼醇（12,13,14）已经开发。这种合成的关键特点是能够控制β-酮酯22的立体化学反应，从而得到23或25。三种法尼醇异构体通过先前使用的合成路线的改进版本转化为相应的异构体因子（9,10和11）。这些多肽的生物学评价表明，令人惊讶的是，这三种多肽都具有与含有e -法尼基部分的天然因子几乎相同的活性。
Thea-factor ofSaccharomyces cerevisiaeis a dodecapeptide pheromone (YIIKGVFWDPAC(Farnesyl)-OCH3,1), in which post-translational modification with a farnesyl isoprenoid and carboxymethyl group is required for full biological activity. This peptide has been used as a model system to explore the biological function of the farnesylcysteine moiety, which is found on and required for the biological activity of many key mammalian proteins. The objective of this particular study was the determination of the biological effect of double bond isomerization of the naturalE,E-farnesyl moiety on the biological activity of thea-factor. A unified, stereoselective synthetic route to the three geometric isomers ofE,E-farnesol (12,13, and14) has been developed. The key feature of this synthesis is the ability to control the stereochemistry of triflation of the β-ketoester22to give either23or25. The three farnesol isomers were converted to the corresponding isomerica-factors (9,10and11) via a modified version of a previously utilized synthetic route. Biological evaluation of these peptides indicates that, surprisingly, all three possess nearly equivalent activity to the naturala-factor bearing theE,E-farnesyl moiety.