Pairing short thiol peptides via disulfides builds an 800,000-member synthetic library that yields potent thrombin inhibitors
- Two sets of short thiol-bearing peptides are joined combinatorially through disulfide bonds, so m fragments and n fragments give m × n distinct peptide sequences.
- Acoustic liquid transfer in 1536-well plates formed several pairs per well, enabling functional screening of over 800,000 compounds against thrombin.
- The screen delivered potent thrombin inhibitors; at under 1 kDa, such pairs may suit oral or intracellular targeting.
💡 Points Based on the abstract
Would I trust a disulfide hit? Only after resynthesis. Plasma thiols and glutathione will scramble that bond, so the real deliverable is the pair's pharmacophore: I'd lock it as a thioether or single-chain linker and see if potency holds. Thrombin suits this well, since the S1 and S2/S3 pockets give an obvious two-fragment split to compare against Phe-Pro-Arg-type chemotypes.