A superactive peptidomimetic analog of a farnesylated dodecapeptide yeast pheromone.
A superactive peptidomimetic analog of a farnesylated dodecapeptide yeast pheromone.
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法尼基化十二肽酵母信息素的超活性拟肽类似物。
DOI：
10.1006/bbrc.1996.1028
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发表时间：
1996
影响因子：
3.1
通讯作者：
Naider,F
中科院分区：
文献类型：
--
作者：
Zhang,YL;Dawe,AL;Jiang,Y;Becker,JM;Naider,F
帖前酿酒酵母交配因子YIIKGVFWDPAC（s-farnesyl）-OCH_3是酿酒酵母中两种介导细胞间信息传递的肽类交配信息素之一，我们以前报道过用d-Ala取代Gly_5使活性增加4-6倍，而用el-Ala_5取代Gly_5则使活性降低4 - 16倍。为了阐明这些发现的结构意义，我们通过插入γ-内酰胺限制代替Lys 4Gly 5或Gly 5Val 6二肽单元，在构象上限制了信息素的中心。用（R）-3-氨基-2-氧代-1-吡咯烷乙酸代替Lys 4Gly 5，得到一种超活性激动剂，其生物活性比α-因子高32倍。相反，用（S）-3-氨基-2-氧代-1-吡咯烷乙酸代替Gly 5Val 6的类似物的活性比α-因子低约30至60倍。这些数据有力地表明，茶因子采用反转作为其生物活性构象。
TheS. cerevisiaea-factor, YIIKGVFWDPAC(s-farnesyl)-OCH3, is one of two peptide mating pheromones which mediate cell-cell communication inS. cerevisiae.We previously reported that replacing Gly5withd-Ala led to a 4–6 fold increase in activity while thel-Ala5homolog was 4 to 16-fold less active than the wildtype. To clarify the structural implications of these findings, we conformationally restricted the center of the pheromone by inserting γ-lactam constraints in place of either the Lys4Gly5or the Gly5Val6dipeptide unit. Incorporation of (R)-3-amino-2-oxo-1-pyrrolidineacetic acid in place of Lys4Gly5led to a super-active agonist which exhibited a 32-fold higher bioactivity than that of thea-factor. In contrast, an analog with (S)-3-amino-2-oxo-1-pyrrolidineacetic acid in place of Gly5Val6is about 30 to 60-fold less active than thea-factor. These data strongly suggest that thea-factor adopts a reverse turn as its bioactive conformation.