We previously reported l-α-aminooxy-phenylpropionic acid (AOPP) to be an inhibitor of auxin biosynthesis, but its precise molecular target was not identified. In this study we found that AOPP targets TRYPTOPHAN AMINOTRANSFERASE of ARABIDOPSIS 1 (TAA1). We then synthesized 14 novel compounds derived from AOPP to study the structure-activity relationships of TAA1 inhibitors in vitro. The aminooxy and carboxy groups of the compounds were essential for inhibition of TAA1 in vitro. Docking simulation analysis revealed that the inhibitory activity of the compounds was correlated with their binding energy with TAA1. These active compounds reduced the endogenous indole-3-acetic acid (IAA) content upon application to Arabidopsis seedlings. Among the compounds, we selected 2-(aminooxy)-3-(naphthalen-2-yl)propanoic acid (KOK1169/AONP) and analyzed its activities in vitro and in vivo. Arabidopsis seedlings treated with KOK1169 showed typical auxin-deficient phenotypes, which were reversed by exogenous IAA. In vitro and in vivo experiments indicated that KOK1169 is more specific for TAA1 than other enzymes, such as phenylalanine ammonia-lyase. We further tested 41 novel compounds with aminooxy and carboxy groups to which we added protection groups to increase their calculated hydrophobicity. Most of these compounds decreased the endogenous auxin level to a greater degree than the original compounds, and resulted in a maximum reduction of about 90% in the endogenous IAA level in Arabidopsis seedlings. We conclude that the newly developed compounds constitute a class of inhibitors of TAA1. We designated them 'pyruvamine'.

中文翻译：

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氨氧基萘丙酸及其衍生物是针对l-色氨酸氨基转移酶的生长素生物合成抑制剂：构效关系。

我们先前曾报道过l-α-氨基氧基-苯丙酸（AOPP）是生长素生物合成的抑制剂，但尚未确定其精确的分子靶标。在这项研究中，我们发现AOPP靶向ARABIDOPSIS 1（TAA1）的TRYPTOPHAN氨基转移酶。然后，我们合成了14种衍生自AOPP的新型化合物，以研究TAA1抑制剂在体外的构效关系。化合物的氨氧基和羧基对于体外抑制TAA1是必不可少的。对接模拟分析表明，化合物的抑制活性与其与TAA1的结合能相关。这些活性化合物在施用到拟南芥幼苗上后降低了内源吲哚-3-乙酸（IAA）的含量。在这些化合物中，我们选择了2-（氨基氧基）-3-（萘-2-基）丙酸（KOK1169 / AONP），并分析了其在体内和体外的活性。用KOK1169处理的拟南芥幼苗表现出典型的生长素缺乏型，并被外源IAA逆转。体外和体内实验表明，KOK1169对TAA1的特异性高于其他酶，例如苯丙氨酸氨裂合酶。我们进一步测试了41种具有氨氧基和羧基的新型化合物，并向其中添加了保护基以增加其疏水性。这些化合物中的大多数将内源性植物生长素水平降低的程度大于原始化合物，并导致拟南芥幼苗中内源性IAA含量最大降低约90％。我们得出的结论是，新开发的化合物构成了一类TAA1抑制剂。