Synthesis of Two Closely Spaced Cysteine Barbiturates Containing Peptides by Copper Catalyzed Oxidation of Contryphan Disulfide

In this report, we are documenting synthesis of peptide barbiturate through copper catalyzed oxidation of peptide disulfide. Single disulfide containing contryphans are used as models to access possibility of anchoring of barbituric acid on to the peptide disulfide. Current method permits anchoring of two molecules of barbituric acid on to the polypeptide and yield of peptide barbiturates varies from 59-84%. Formation of cysteine sulfenic acid (Cys-SOH) during oxidation of disulfide was confirmed using chemical probe of Cys-SOH dimedone. Mass spectrometric studies have confirmed presence of cysteine barbiturate in anchored peptides. Based on nature of reactive oxygen species involved in oxidation of peptide disulfide, possible mechanisms were proposed for anchoring of barbituric acid on to the peptide disulfide through Cys-SOH. This is first report on anchoring of two molecules of barbituric acid on to the closely spaced cysteine residues of single polypeptide.