title: High-throughput screening of small molecule ligands targeted to live bacteria surface.
abstract: 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 in. × 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-magenta-yellow-key (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.
authors: Center for Molecular Imaging, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States.
authors: Jeong Heon
authors: JH
authors: Lee
authors: Sunny
authors: S
authors: Park
authors: Hoon
authors: H
authors: Hyun
authors: Mark W
authors: MW
authors: Bordo
authors: Rafiou
authors: R
authors: Oketokoun
authors: Khaled A
authors: KA
authors: Nasr
authors: John V
authors: JV
authors: Frangioni
authors: Hak Soo
authors: HS
authors: Choi
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000166:cytology / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D008024:Ligands; D054852:Small Molecule Libraries