Department of Chemistry, Umeå University, 90187 Umeå, Sweden.
Chemistry. 2012 Apr 10;18(15):4522-32. doi: 10.1002/chem.201103936. Epub 2012 Mar 16.
Pilicides and curlicides are compounds that block the formation of the virulence factors pili and curli, respectively. To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized. This was achieved by using a strategy based on structure-activity knowledge, in which key pilicide and curlicide substituents on the ring-fused dihydrothiazolo 2-pyridone central fragment were replaced by fluorophores. Several of the resulting fluorescent compounds had improved activities as measured in pili- and curli-dependent biofilm assays. We created fluorescent pilicides and curlicides by introducing coumarin and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores at two positions on the peptidomimetic pilicide and curlicide central fragment. Fluorescence images of the uropathogenic Escherichia coli (UPEC) strain UTI89 grown in the presence of these compounds shows that the compounds are strongly associated with the bacteria with a heterogeneous distribution.
黏菌素和卷曲菌素是分别阻断毒力因子菌毛和卷曲菌毛形成的化合物。为了便于研究这些化合物与菌毛和卷曲菌毛组装系统之间的相互作用，已经合成了荧光黏菌素和卷曲菌素。这是通过使用基于结构-活性知识的策略来实现的，其中将环状二氢噻唑并[2,3-p]吡啶酮中心片段上的关键黏菌素和卷曲菌素取代基替换为荧光团。在依赖菌毛和卷曲菌毛的生物膜测定中，所得到的一些荧光化合物的活性得到了提高。我们通过在肽模拟黏菌素和卷曲菌素的中心片段的两个位置引入香豆素和 4,4-二氟-4-硼-3a,4a-二氮杂-s-茚（BODIPY）荧光团来创建荧光黏菌素和卷曲菌素。在存在这些化合物的情况下生长的尿路致病性大肠杆菌（UPEC）菌株 UTI89 的荧光图像表明，这些化合物与细菌强烈相关，分布不均匀。
