Sulfamylbutyryl resins
Sulfamylbutyryl resins facilitate the preparation by Fmoc SPPS of the C-terminal peptide thioesters required for native thiol ligation.
The resin-bound sulfamyl group is acylated by carboxylic acids activated with PyBOP and DIPEA in CHCl3 at -20 °C or DIPCDI and N-methylimidazole in DCM. It can be sometimes problematic to obtain acceptable loadings by these methods, and so it is for this reason that Novabiochem now offers a number of pre-loaded sulfamylbutyryl resins.
The resin-bound acylsulfonamide is completely stable to basic or strongly nucleophilic reagents, making it compatible with Fmoc SPPS.
Following completion of the synthesis, the sulfonamide can be activated by methylation with TMS-CHN2, and then cleaved with ethyl mercaptopropionate in the presence of sodium thiophenolate, to yield the appropriate thioester. Alternatively, activation can be performed with iodoacetonitrile/DIPEA and cleavage by benzylmercaptan. Following removal of side-chain protecting groups with TFA, this material can be used for native thiol ligation.
