Synthesis of two closely spaced cysteine barbiturates containing peptides by copper-catalyzed oxidation of contryphan disulfide

ABSTRACT

In this report, we are documenting the 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 (BRB) onto the peptide disulfide. Current method permits anchoring of two molecules of BRB onto the polypeptide and yield of peptide barbiturates varies from 59 to 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 the presence of cysteine barbiturate in anchored peptides. Based on the nature of reactive oxygen species involved in oxidation of peptide disulfide, possible mechanisms were proposed for anchoring of BRB onto the peptide disulfide through Cys-SOH. This is the first report on anchoring of two molecules of BRB onto the closely spaced cysteine residues of single polypeptide.

GRAPHICAL ABSTRACT

KEYWORDS:

• Barbituric acid
• contryphan
• cysteine barbiturate
• cysteine sulfenic acid
• mass spectrometry
• peptide disulfide

Acknowledgment

This article is dedicated to 68th birth day celebration of Prof. P. Balaram (MBU, IISc, Bangalore, India). KHG acknowledges DST-INSPIRE faculty fellowship (LSBM-003). PChVG is supported by the award of a Junior Research Fellowship from the University Grant Commission, India. We acknowledge the help of Mrs. Sunitha and Mr. Shashanka Rao. We also acknowledge proteomic facility of MBU-IISc, India.