Initiating DNA-Encoded Library Synthesis with a Hexathymidine DNA Oligonucleotide.

Libraries of DNA-encoded compounds (DELs) are a validated screening technology for drug discovery. Here we describe a library synthesis strategy that starts with a solid phase-bound, chemically very stable hexathymidine DNA sequence "hexT." Different heterocycle conjugates of the hexT oligonucleotide were synthesized from simple starting materials using metal or acid catalysts. The hexT conjugates were isolated, characterized, and ligated to coding DNA sequences.