Decker Daniel, Öberg Christopher, Kleczkowski Leszek A
a Department of Plant Physiology , Umeå Plant Science Center, Umeå University , Umeå , Sweden.
b Laboratories for Chemical Biology Umeå, Department of Chemistry , Umeå University , Umeå , Sweden.
Plant Signal Behav. 2018;13(8):e1507406. doi: 10.1080/15592324.2018.1507406. Epub 2018 Aug 20.
UDP-sugars are key precursors for biomass production in nature (synthesis of cellulose, hemicellulose, etc.). They are produced de novo by distinct UDP-sugar producing pyrophosphorylases. Studies on the roles of these enzymes using genetic knockouts were hampered by sterility of the mutants and by functional-complementation from related enzyme(s), hindering clear interpretation of the results. In an attempt to override these difficulties, we turned to the reverse chemical genetics approaches to identify compounds which interfere with the activity of those enzymes in vivo. Hit expansion on one of such compounds, a salicylimide derivative, allowed us to identify several inhibitors with a range of activities. The present study provides a structure-activity relationship for these compounds.
UDP-糖是自然界中生物质生产（纤维素、半纤维素等的合成）的关键前体。它们由不同的UDP-糖生产焦磷酸化酶从头合成。使用基因敲除研究这些酶的作用受到突变体不育以及相关酶功能互补的阻碍，妨碍了对结果的清晰解释。为了克服这些困难，我们转向反向化学遗传学方法来鉴定体内干扰这些酶活性的化合物。对其中一种化合物（水杨酰亚胺衍生物）进行命中扩展，使我们能够鉴定出几种具有一系列活性的抑制剂。本研究提供了这些化合物的构效关系。
