Instituto de Tecnologia Química e Biológica, Av. da República, Estação Agronómica Nacional, 2780-157 Oeiras, Portugal.
Bioorg Med Chem. 2012 Jan 1;20(1):249-56. doi: 10.1016/j.bmc.2011.11.007. Epub 2011 Nov 12.
Bacteria coordinate population-dependent behaviors such as virulence by intra- and inter-species communication (quorum sensing). Autoinducer-2 (AI-2) regulates inter-species quorum sensing. AI-2 derives from the spontaneous cyclisation of linear (S)-4,5-dihydroxypentanedione (DPD) into two isomeric forms in dynamic equilibrium. Different species of bacteria have different classes of AI-2 receptors (LsrB and LuxP) which bind to different cyclic forms. In the present work, DPD analogs with a new stereocenter at C-5 (4,5-dihydroxyhexanediones (DHDs)) have been synthesized and their biological activity tested in two bacteria. (4S,5R)-DHD is a synergistic agonist in Escherichia coli (which contains the LsrB receptor), while it is an agonist in Vibrio harveyi (LuxP), displaying the strongest agonistic activity reported so far (EC(50)=0.65μM) in this organism. Thus, modification at C-5 opens the way to novel methods to manipulate quorum sensing as a method for controlling bacteria.
细菌通过种内和种间通讯（群体感应）协调依赖于种群的行为，如毒力。自动诱导物-2（AI-2）调节种间群体感应。AI-2 源自线性（S）-4,5-二羟基戊二酮（DPD）的自发环化，在动态平衡中形成两种互变异构体。不同种类的细菌具有不同类别的 AI-2 受体（LsrB 和 LuxP），它们与不同的环状形式结合。在本工作中，在 C-5 位具有新的手性中心的 DPD 类似物（4,5-二羟基己二酮（DHDs））已被合成，并在两种细菌中测试了它们的生物学活性。（4S,5R）-DHD 是大肠杆菌（含有 LsrB 受体）的协同激动剂，而在 Harveyi 弧菌（LuxP）中，它是激动剂，在该生物体中显示出迄今为止报道的最强激动活性（EC50=0.65μM）。因此，C-5 位的修饰为操纵群体感应开辟了新的方法，作为控制细菌的方法。
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