Hybrid Stereoisomers of a Compact Molecular Probe Based on a Jasmonic Acid Glucoside: Syntheses and Biological Evaluations
Hybrid Stereoisomers of a Compact Molecular Probe Based on a Jasmonic Acid Glucoside: Syntheses and Biological Evaluations
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基于茉莉酸葡萄糖苷的紧凑分子探针的杂化立体异构体：合成和生物学评价
DOI：
10.1016/j.bmc.2012.08.003
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
M. Ueda
中科院分区：
文献类型：
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作者：
Akinori Saito;Tsuyoshi Takahashi;M. Ueda
12-O-β-d-吡喃葡萄糖基茉莉酸（12-O-β-d-glucopyranosyl jasmonic acid，JAG）具有独特的生物活性，其中包括对Samanea saman的叶片关闭作用。预计这种调节的作用方式与其他茉莉酸酯不同。我们开发了基于JAG的高性能紧凑分子探针（CMPs），可用于JAG靶标的FLAG标记。我们合成了四个混合型JAG-CMP立体异构体（7，ent-7，8和ent-8），它们分别由（-）-12-OH-JA（2）/d-吡喃半乳糖苷、（-）-2/1-吡喃半乳糖苷、（+）-ent-2/d-吡喃半乳糖苷和（+）-ent-2/1-吡喃半乳糖苷部分组成，并且我们检查了它们的生物学特征，例如收缩的立体特异性诱导，细胞反应速率和对钾通道活性的依赖性。JAG-CMP的这些特征与最初的JAG完全一致。这些结果表明JAG和JAG-CMP具有生物等效性。在这种生物学评价的过程中，揭示了CMP的生物活性极大地依赖于糖基部分的d/l-立体化学。据我们所知，这是第一个研究表明，d/l-立体化学的糖基部分显着影响相关糖苷的生物活性。
12-O-β-d-glucopyranosyl jasmonic acid (JAG) shows unique biological activities, including leaf-closing of Samanea saman. It is expected that the mode of action for such regulation is distinct from that of other jasmonates. We developed high-performance compact molecular probes (CMPs) based on JAG that can be used for the FLAG-tagging of JAG target. We synthesized four hybrid-type JAG-CMP stereoisomers (7, ent-7, 8, and ent-8), which are composed of (−)-12-OH-JA (2)/d-galactopyranoside, (−)-2/l-galactopyranoside, (+)-ent-2/d-galactopyranoside, and (+)-ent-2/l-galactopyranoside moieties, respectively, and we examined their biological features, such as the stereospecific induction of shrinkage, rate of the cellular response, and dependence on potassium channel activity. These features of the JAG-CMPs were completely consistent with those of the original JAG. These results indicate the biological equivalence of JAG and the JAG-CMPs. During the course of such biological evaluations, it was revealed that the biological activity of the CMPs is greatly dependent on the d/l-stereochemistry of a glycon moiety. To the best of our knowledge, this is the first study suggesting that the d/l-stereochemistry of the glycon moiety significantly affects the biological activity of the associated glycoside.