title: The Cysteine S-Alkylation Reaction as a Synthetic Method to Covalently Modify Peptide Sequences.
abstract: Synthetic methodologies to chemically modify peptide molecules have long been investigated for their impact in the field of chemical biology. They allow the introduction of biochemical probes useful for studying protein functions, for manipulating peptides with therapeutic potential, and for structure-activity relationship investigations. The commonly used approach was the derivatization of an amino acid side chain. In this regard, the cysteine, for its unique reactivity, has been widely employed as the substrate for such modifications. Herein, we report on methodologies developed to modify the cysteine thiol group through the S-alkylation reaction. Some procedures perform the alkylation of cysteine derivatives, in order to prepare building blocks to be used during the peptide synthesis, whilst some others selectively modify peptide sequences containing a cysteine residue with a free thiol group, both in solution and in the solid phase.
authors.affiliation: Institute of Biostructures and Bioimaging, National Research Council, Via Mezzocannone, 16, 80134, Naples, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Calce
authors.affiliation: Institute of Biostructures and Bioimaging, National Research Council, Via Mezzocannone, 16, 80134, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: De Luca
mesh_terms: D000478:Alkylation; D000595:Amino Acid Sequence; D000641:Ammonia / Q000737:chemistry; D001388:Aziridines / Q000737:chemistry; D002384:Catalysis; D003545:Cysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D019345:Zinc Acetate / Q000737:chemistry
chemical_list: D001388:Aziridines; D010455:Peptides; D013438:Sulfhydryl Compounds; C033132:aziridine; D000641:Ammonia; D012964:Sodium; D019345:Zinc Acetate; D003545:Cysteine
keywords: cysteine thio-alkylation; peptides; solid-phase synthesis; solution-phase synthesis; unnatural amino acids