The properties of S-benzyloxymethylcysteine, Cys(Bom), were examined. The S-Bom group is stable to trifluoroacetic acid (TFA), but is easily cleaved by treatment with silver trifluoromethanesulfonate (AgOTf)/TFA or 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf)-thioanisole/TFA. Cys(Bom) can be converted to cystine by treatment with thallium(lll) triffuoroacetate. Cys(Bom) was successfully applied to the Fmoc-based solid phase synthesis of porcine brain natriuretic peptide (pBNP), a 26-residue peptide with one disulfide bond [Fmoc.9-fluorenylmethytoxycarbonyl]. In the final step, the peptide-resin was first treated with AgOTf/TFA, then with 1 M trimethylsilyl bromide-thioanisole/TFA. After dithiothreitol treatment and subsequent air-oxidation, a homogeneous pBNP was obtained in 17% yield, based on the first amino acid loaded on the resin. The result was compared with those produced by other alternative deprotecting procedures.
ASJC Scopus subject areas
- Drug Discovery