Automated solid-phase synthesis feeds crude libraries straight into assays, speeding CCR2 hit optimisation in two cycles
- Solution-phase direct-to-biology is limited to a few assay-compatible reactions. This platform runs multistep resin-bound chemistry on an automated system and assays the crude cleaved products unpurified.
- Across several chemotypes of allosteric CCR2 ligands, affinity rankings of crude samples tracked those of purified compounds.
- On a little-explored CCR2 hit, it sampled over 1,700 building-block combinations and gave improved binders in two DMTA cycles.
💡 Points Based on the abstract
Crude and purified rankings agreeing is encouraging, but truncated sequences, residual TFA or scavenger-derived impurities could behave differently in a binding assay for a lipophilic GPCR allosteric site, where sticky contaminants can fake affinity. Resynthesise the top few, confirm purified affinity and ligand efficiency, and check the SAR survives solution-phase scale-up.
📄 Paper · chemRxiv ↗ AutoSPS-D2B: Automated Solid-Phase Synthesis Expands the Reaction Scope for Direct-to-Biology Libraries