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

Chenggang Zhu; Xiangdong Zhu; James P Landry; Zhaomeng Cui; Quanfu Li; Yongjun Dang; Lan Mi; Fengyun Zheng; Yiyan Fei

doi:10.3390/s16030378

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

Sensors (Basel). 2016 Mar 16;16(3):378. doi: 10.3390/s16030378.

Authors

Chenggang Zhu¹, Xiangdong Zhu², James P Landry³, Zhaomeng Cui⁴, Quanfu Li⁵, Yongjun Dang⁶, Lan Mi⁷, Fengyun Zheng⁸, Yiyan Fei⁹

Affiliations

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. 13210720017@fudan.edu.cn.
² Department of Physics, University of California, Davis, CA 95616, USA. xdzhu@physics.ucdavis.edu.
³ Department of Physics, University of California, Davis, CA 95616, USA. jim.landry@gmail.com.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. zhengfengyun@outlook.com.
⁹ 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.

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%.

Keywords: high-throughput screening; label-free optical biosensor; small-molecule microarrays; surface functionalization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Discovery*
Glass / chemistry
Humans
Isocyanates / chemistry*
Microarray Analysis*
Small Molecule Libraries / chemistry*
Small Molecule Libraries / pharmacology

Substances

Isocyanates
Small Molecule Libraries