title: Developing an Efficient and General Strategy for Immobilization of Small Molecules onto Microarrays Using Isocyanate Chemistry.
abstract: Small-molecule microarray (SMM) is an effective platform for identifying lead compounds from large collections of small molecules in drug discovery, and efficient immobilization of molecular compounds is a pre-requisite for the success of such a platform. On an isocyanate functionalized surface, we studied the dependence of immobilization efficiency on chemical residues on molecular compounds, terminal residues on isocyanate functionalized surface, lengths of spacer molecules, and post-printing treatment conditions, and we identified a set of optimized conditions that enable us to immobilize small molecules with significantly improved efficiencies, particularly for those molecules with carboxylic acid residues that are known to have low isocyanate reactivity. We fabricated microarrays of 3375 bioactive compounds on isocyanate functionalized glass slides under these optimized conditions and confirmed that immobilization percentage is over 73%.
authors.affiliation: Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai 200433, China. 13210720017@fudan.edu.cn.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Physics, University of California, Davis, CA 95616, USA. xdzhu@physics.ucdavis.edu.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Physics, University of California, Davis, CA 95616, USA. jim.landry@gmail.com.
authors.forename: James P
authors.initials: JP
authors.lastname: Landry
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. 15111010017@fudan.edu.cn.
authors.forename: Zhaomeng
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. lqfmic@gmail.com.
authors.forename: Quanfu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. yongjundang@fudan.edu.cn.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai 200433, China. lanmi@fudan.edu.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Mi
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. zhengfengyun@outlook.com.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai 200433, China. fyy@fudan.edu.cn.
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Fei
mesh_terms: D055808:Drug Discovery; D005898:Glass / Q000737:chemistry; D006801:Humans; D017953:Isocyanates / Q000737:chemistry*; D046228:Microarray Analysis; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D017953:Isocyanates; D054852:Small Molecule Libraries
keywords: high-throughput screening; label-free optical biosensor; small-molecule microarrays; surface functionalization