High-Throughput Binder Confirmation (HTBC).

In this chapter, we describe a DEL "recipe" approach to hit confirmation using on-DNA cleavable linkers which can be followed by direct AS-MS evaluation and identification of binder(s) from the released small-molecule mixture. When coupled with automation, this platform creates opportunity for enabling an even higher-throughput binder confirmation (HTBC) platform to allow full interrogation of selections results. Two on-DNA cleavable strategies of releasing small molecules from DNA are reported herein.