High-Throughput Screening of Small Molecule Ligands Targeted to Live Bacteria Surface

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• 作者：Jeong Heon Lee ; Sunny Park ; Hoon Hyun ; Mark W. Bordo ; Rafiou Oketokoun ; Khaled A. Nasr ; John V. Frangioni ; Hak Soo Choi
• 刊名：Analytical Chemistry
• 出版年：2013
• 出版时间：April 2, 2013
• 年：2013
• 卷：85
• 期：7
• 页码：3508-3514
• 全文大小：528K
• 年卷期：v.85,no.7(April 2, 2013)
• ISSN：1520-6882

文摘

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 渭m diameter chemical spots in a 1 in. 脳 3 in. nanolayered 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鈥搈agenta鈥搚ellow鈥搆ey (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.