Efficient Palladium‐Assisted One‐Pot Deprotection of (Acetamidomethyl)Cysteine Following Native Chemical Ligation and/or Desulfurization To Expedite Chemical Protein Synthesis. Issue 28 (29th April 2016)

• Record Type: Journal Article
• Authors: Maity, Suman Kumar; Jbara, Muhammad; Laps, Shay; Brik, Ashraf
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 28(2016)
• Page Start: 8108
• Page End: 8112
• Publication Date: 2016-04-29
• Subjects: cysteine -- desulfurization -- native chemical ligation -- palladium -- protein synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201603169
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The acetamidomethyl (Acm) moiety is a widely used cysteine protecting group for the chemical synthesis and semisynthesis of peptide and proteins. However, its removal is not straightforward and requires harsh reaction conditions and additional purification steps before and after the removal step, which extends the synthetic process and reduces the overall yield. To overcome these shortcomings, a method for rapid and efficient Acm removal using Pd II complexes in aqueous medium is reported. We show, for the first time, the assembly of three peptide fragments in a one‐pot fashion by native chemical ligation where the Acm moiety was used to protect the N‐terminal Cys of the middle fragment. Importantly, an efficient synthesis of the ubiquitin‐like protein UBL‐5, which contains two native Cys residues, was accomplished through the one‐pot operation of three key steps, namely ligation, desulfurization, and Acm deprotection, highlighting the great utility of the new approach in protein synthesis. Abstract : Three in one : An efficient method for the deprotection of (acetamidomethyl)cysteine using Pd complexes in aqueous medium was introduced and applied to the one‐pot assembly of three peptides. UBL‐5 was thus synthesized by one‐pot native chemical ligation, desulfurization, and removal of the acetamidomethyl (Acm) group while keeping its two native Cys residues intact.