In vitro selection assays of encoded libraries allow for a collective querying of function for many molecules simultaneously. This approach has several advantages over assays employed in traditional small molecule screening, including much improved throughput and dramatically lower cost. We present an evaluation of in vitro selection assays with regard to their application to discovery from DNA-encoded libraries (DELs). We explored both traditional as well as crosslinking-based selections to the chromodomains of the CBX family. We present a quantitative evaluation of selection assay robustness using DNA-linked ligands of known afffinity. Statistical analysis of assays indicated low DNA tag bias and adequate robustness for both ligand discovery and deterination of quantitative structure activity relationships. Implementation of optimal assays were employed with iterative "design, build, test" cycles of DNA-encoded libraries, which were assayed in parallel against all members of the CBX family. We present progress with isoform selective ligands in cellular assays, particulary with inhibition of growth of select cancer cell lines.

<i>In vitro</i> selection assays: On-DNA medicinal chemistry optimization of peptidomimetic ligands to chromodomains

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

In vitro selection assays: On-DNA medicinal chemistry optimization of peptidomimetic ligands to chromodomains