Novel electrochemically-mediated peptide dethiylation in processes relevant to native chemical ligation

Abstract

Here we explore electrochemical dethiylation in processes relevant to Native Chemical Ligation (NCL). NCL’s reliance on the redox active amino acid cysteine and β-mercaptoamine derivatives suggests a potential role for...

Investigation of acyl transfer auxiliary-assisted glycoconjugation for glycoprotein semi-synthesis

“…19 was prepared in a similar manner to 15, employing reductive amination between 13 and aldehyde 20. 25 19 was obtained upon exposure of 21 to triethylsilane and TFA in DCM. To make progress towards protein glycosylation we further examined ligation reactions between 15 or 19 and free ThioD and reactions were complete within 24 h (see supporting information).…”

Electrochemistry-enabled residue-specific modification of peptides and proteins

“…Recently, Macmillan and co-workers reported an excellent protocol for desulfurization of the cysteine side chain (Scheme 2X) by applying 1 V vs. Ag/AgCl in an undivided cell containing platinum electrodes in 4 : 1 H 2 O/ MeCN solvent containing 0.1 M sodium phosphate buffer ( pH = 5.8) in the presence of 0.15 M tris-carboxyethyl phosphine (TCEP). 84 The authors acquired evidence in favour of a radical mechanism (Scheme 2Y). The mercapto group of compound 6 imparts an electron to the Pt-anode to generate a reactive species 8, which forms intermediate 9 in conjugation with TCEP.…”

“…Recently, Macmillan and co-workers reported an excellent protocol for desulfurization of the cysteine side chain (Scheme 2X) by applying 1 V vs. Ag/AgCl in an undivided cell containing platinum electrodes in 4 : 1 H 2 O/MeCN solvent containing 0.1 M sodium phosphate buffer (pH = 5.8) in the presence of 0.15 M tris-carboxyethyl phosphine (TCEP). 84…”

An Iron‐Catalyzed Protein Desulfurization Method Reminiscent of Aquatic Chemistry

“…This method is particularly popular and accounts for the majority of the desulfurization reactions performed today [3] . Conceptually, the majority of the Cys desulfurization methods designed afterwards also rely on the powerfulness of TCEP to combine with Cys thiyl radicals (Figure 1b), but differ by the way the latter are generated using either chemical (boron compounds), [7] photochemical (UV light irradiation, [8] light irradiation in the presence of ruthenium or iridium metal complexes) [9] or electrochemical [10] methods.…”