High-throughput screening of small molecule ligands targeted to live bacteria surface.

High-throughput screening of small molecule ligands targeted to live bacteria surface.
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DOI:
10.1021/ac303199x
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发表时间:
2013-04-02
影响因子:
7.4
通讯作者:
Choi, Hak Soo
Choi, Hak Soo
中科院分区:
化学1区
文献类型:
--
作者:
Lee, Jeong Heon;Park, Sunny;Hyun, Hoon;Bordo, Mark W.;Oketokoun, Rafiou;Nasr, Khaled A.;Frangioni, John V.;Choi, Hak Soo

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针对活病原菌表面的小分子配体的发现将使一类全新的抗生素成为可能。我们报告了一个基于微阵列的细菌高通量筛选平台的开发和验证,该平台利用1 "× 3"纳米层状载玻片格式中直径为300 μ m的化学斑点。使用24种模型化合物和4种不同的细菌菌株,我们优化了筛选技术,包括基于荧光团的光学去卷积用于亲和力的自动评分和用于亲和力和特异性评分的青色-洋红色-黄色-黑色(CMYK)颜色编码。后者提供了多维数据的无损一维视图。通过将计算机模拟分析与细胞结合亲和力和特异性联系起来,我们也可以开始鉴定影响配体性能的物理化学因素。我们所描述的技术可以为开发新型抗生素奠定基础。
The discovery of small molecule ligands targeted to the surface of live pathogenic bacteria would enable an entirely new class of antibiotics. We report the development and validation of a microarray-based high-throughput screening platform for bacteria that exploits 300 μm diameter chemical spots in a 1” × 3” nano-layered glass slide format. Using 24 model compounds and 4 different bacterial strains we optimized the screening technology, including fluorophore-based optical deconvolution for automated scoring of affinity and cyan-magenta-yellow-black (CMYK) color-coding for scoring of both affinity and specificity. The latter provides a lossless, one-dimensional view of multidimensional data. By linking in silico analysis with cell binding affinity and specificity, we could also begin to identify the physicochemical factors that affect ligand performance. The technology we describe could form the foundation for developing new classes of antibiotics.
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