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ACS Comb Sci. 2017 Apr 10;19(4):255-261. doi: 10.1021/acscombsci.6b00181. Epub 2017 Mar 6.

Encoded Silicon-Chip-Based Platform for Combinatorial Synthesis and Screening.

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Department of Chemistry, Yale University , 225 Prospect Street, New Haven, Connecticut 06511, United States.


Solid-supported chemical libraries have proven useful for the rapid and cost-effective discovery of bioactive compounds. However, traditional on-bead screening involves time-intensive chemical characterization of hit compounds and high false positive rates. Herein, we report a new platform for encoded chemical synthesis and solid-supported screening using p-Chips, microsized silicon microtransponders capable of storing and emitting unique numerical identifiers (IDs). By encoding the structures of library members using p-Chip IDs, we can track compound identities throughout both split-and-pool synthesis and protein binding assays without destructive cleavage. Thanks to the numerical IDs, our p-Chip platform can provide binding constants for library members simply by stripping and reprobing with different protein concentrations, unlike traditional on-bead assays. To showcase these features, we synthesized a library of 108 hemagglutinin (HA) peptide variants using split-and-pool approach, and measured EC50s for each variant directly on p-Chips. On-chip EC50s obtained from these studies showed excellent correlation (80%) with those obtained using traditional ELISA methods. Our screen also yielded a false positive rate of 14%, markedly superior to that reported for conventional bead-based binding studies (66-96%).1-9 On the basis of these results, we believe the p-Chip platform has the potential to improve the effectiveness of solid-supported high-throughput screening by a significant margin.


combinatorial chemistry; peptide library; radiofrequency identification (RFID); silicon chips; split-and-pool synthesis

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