Solid-phase synthesis of Stat3 inhibitors incorporating O-carbamoylserine and O-carbamoylthreonine as glutamine mimics

Article abstract of DOI:10.1016/j.bmcl.2006.10.099

O-Carbamoylserine and O-carbamoylthreonine are glutamine analogues that were incorporated into a Stat3 inhibitory peptide to probe the requirements of Gln at the pY+3 position. Fmoc-Ser-NHBn and Fmoc-Thr-NHBn were converted to nitrophenyl carbonates and were attached to Rink resin via a side-chain carbamate linkage. After assembly of the peptide, acid treatment resulted in O-carbamoylserine and O-carbamoylthreonine-containing peptides. The order of affinity for Stat3 was Gln > Ser(CONH₂) ? Thr(CONH₂) suggesting a relatively tight binding pocket for the side chain of glutamine.