Automated peptide-resin deprotection/cleavage by a robotic workstation.

A robotic workstation has been constructed that automates the deprotection of peptides with trifluoroacetic acid-labile side-chain protecting groups and cleavage from acid-labile resins. The workstation was constructed around a Zymark robot arm and is integrated with a peptide synthesis workstation. Peptide resin samples are deprotected and cleaved with a trifluoroacetic acid/scavenger cocktail that accommodates all common protecting groups used with Fmoc chemistry. Aqueous-ether continuous extraction is used to remove the scavengers and reaction by-products. The apparatus cleaves a 50-500-mg sample of peptide resin every 2 hours and provides the peptides as an aqueous solution in 10% HOAc. Crude peptides obtained with this apparatus are free from residual scavengers and range in yield from 50%-80%. This method is applicable to all but the most hydrophobic peptides and minimizes human contact with the noxious cleavage reagents.