Magnetic anion-exchange resin enables automated DNA-encoded library synthesis
- An unreviewed preprint describes a robotic workflow that automates split-and-pool, the step in DNA-encoded library synthesis usually done by hand.
- DNA conjugates are captured on a weak anion-exchange magnetic resin and shuttled between steps by a particle handler, allowing on-DNA amide coupling, reductive amination, click chemistry and Fmoc deprotection in organic solvent.
- Two-cycle libraries of several thousand members were made, and control selections consistently recovered a known carbonic anhydrase binder.
💡 Points
Two cycles and a few thousand members is a toy library, and recovering carbonic anhydrase proves little; it's the easiest control in DEL. The numbers that matter are yield and DNA integrity per on-resin step, since organic-solvent chemistry only pays off if it opens reactions aqueous conditions can't, like Pd couplings or SNAr. Automation helps reproducibility, not diversity.
Automated DNA-Encoded Library Synthesis on Magnetic Anion Exchange Resin ↗