A Homogenous Small Molecule Microarray for Enzymatic Assays

摘要

Small molecule microarray as an emerging technology promises to play a pivotal role in chemical genetics. However, in spite of the fast development of this technology special requirements, such as the immobilization of small molecules on the chip surface limit the utilization of microarray. We have developed a unique homogenous microarray system that can be used to array any small chemical compounds, in addition of peptides and proteins without pre-immobilization. A standard microscope slide containing up to 5000 microarray dots, with volumes less than 2 nanoliter each and acting as individual reaction centers, can be printed with standard DNA arrayer. An aerosol deposition technology was adapted to deliver extremely small volumes of biofluids uniformly into each reaction center. The following biochemical reactions are performed in a traditional solution-phase environment. Fluorescence based reaction signals were then scanned and analyzed with standard chip scanner and microarray analyzing software. In this study, we demonstrated that this chip could be used for not only screening individual but also multiple enzymatic activities simultaneously with different fluorescent tagged small peptide libraries. We further demonstrated that this system could be a very powerful ultra high throughput screening tool for drug discovery, with which we have identified potential "hits" after screening chips printed with small chemical compounds against caspases 1 and 3.