Developing an Efficient and General Strategy for Immobilization of Small Molecules onto Microarrays Using Isocyanate Chemistry

Sensors

Yiyan Fei¹  Lan Mi¹  Chenggang Zhu¹  Xiangdong Zhu²  James P. Landry²  Fengyun Zheng³  Yongjun Dang⁴  Zhaomeng Cui⁴  Quanfu Li⁴ 

[1] 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;Department of Physics, University of California, Davis, CA 95616, USA;Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China;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;

关键词: high-throughput screening;    small-molecule microarrays;    surface functionalization;    label-free optical biosensor;   

DOI  :  10.3390/s16030378

来源: DOAJ

【 摘 要 】

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%.

【 授权许可】

Unknown