Synthesis of Peptide Cysteine Dimedone Using Fmoc-Cys(Dmd)-OH: Glutathione Cysteine Dimedone as a Probe in Investigating the Sulfenic Acid Mediated Oxidation of Glutathione

Amarnath Reddy, KK and Moi, S and Dolle, A and Hosamani, B and Krishnamurthy, K and Prakash, S and Raghothama, S and Gowd, KH (2020) Synthesis of Peptide Cysteine Dimedone Using Fmoc-Cys(Dmd)-OH: Glutathione Cysteine Dimedone as a Probe in Investigating the Sulfenic Acid Mediated Oxidation of Glutathione. In: Helvetica Chimica Acta, 103 (7).

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Abstract

Dimedone is the most widely used chemical probe for detection of cysteine sulfenic acid in peptides and proteins. The reaction of dimedone with cysteine sulfenic acid results in the formation of unique cysteine dimedone motif containing thioether bridge. Based on the structure of cysteine dimedone residue in polypeptide, a new building block of Fmoc-Cys(Dmd)-OH was developed for solid phase synthesis of peptide cysteine dimedone. Mass spectrometric sequencing of synthetic peptides have confirmed successful incorporation of cysteine dimedone in peptide chain using HBTU/HOBt as a coupling agent. The new method permits synthesis of peptides containing both cysteine thiol and cysteine dimedone in the same sequence which was difficult to achieve by conventional methods. The synthetic peptide of glutathione cysteine dimedone was used as a standard in probing the air-mediated oxidation of thiol to disulfide form of glutathione. The co-elution of standard peptide and reaction mixture of oxidation of glutathione in presence of dimedone using RP-HPLC have confirmed the formation of glutathione cysteine sulfenic as an intermediate in the air-mediated oxidation of glutathione. The synthetic peptides of cysteine dimedone may find application in the field of redox proteomics and generation of antibodies against modified cysteine residue.

Item Type:	Journal Article
Publication:	Helvetica Chimica Acta
Publisher:	Wiley Blackwell
Additional Information:	The copyright for this article belongs to Wiley Blackwell.
Keywords:	Amino acids; Chemical detection; Coupling agents; Mass spectrometry; Oxidation; Probes; Proteomics; Reaction intermediates; Sulfur compounds; Synthesis (chemical), Building blockes; Chemical probes; Conventional methods; Cysteine residues; Mass spectrometric sequencing; Reaction mixture; Solid phase synthesis; Synthetic peptide, Peptides, 5,5 dimethyl 1,3 cyclohexanedione; cysteine; glutathione derivative; sulfenic acid derivative; synthetic peptide, amino terminal sequence; Article; computational fluid dynamics; controlled study; electrospray mass spectrometry; Fourier transform spectroscopy; human; molecular probe; peptide synthesis; priority journal; proteomics; reversed phase high performance liquid chromatography; room temperature; solid phase synthesis
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Date Deposited:	06 Feb 2023 06:39
Last Modified:	06 Feb 2023 06:39
URI:	https://eprints.iisc.ac.in/id/eprint/79856

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