title: Efficient Palladium-Assisted One-Pot Deprotection of (Acetamidomethyl)Cysteine Following Native Chemical Ligation and/or Desulfurization To Expedite Chemical Protein Synthesis.
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.
authors.affiliation: Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel.
authors.forename: Suman Kumar
authors.initials: SK
authors.lastname: Maity
authors.affiliation: Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Jbara
authors.affiliation: Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Laps
authors.affiliation: Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel. abrik@technion.ac.il.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Brik
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D005136:Eye Proteins / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D010165:Palladium / Q000737:chemistry*; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry; D013455:Sulfur / Q000737:chemistry*; D014452:Ubiquitins / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D005136:Eye Proteins; D011506:Proteins; C429294:UBL5 protein, human; D014452:Ubiquitins; D010165:Palladium; D013455:Sulfur; D003545:Cysteine
keywords: cysteine; desulfurization; native chemical ligation; palladium; protein synthesis