title: Synthesis of Sulfotyrosine-Containing Peptides by Incorporating Fluorosulfated Tyrosine Using an Fmoc-Based Solid-Phase Strategy.
abstract: Tyrosine O-sulfation is a common protein post-translational modification that regulates many biological processes, including leukocyte adhesion and chemotaxis. Many peptides with therapeutic potential contain one or more sulfotyrosine residues. We report a one-step synthesis for Fmoc-fluorosulfated tyrosine. An efficient Fmoc-based solid-phase peptide synthetic strategy is then introduced for incorporating the fluorosulfated tyrosine residue into peptides of interest. Standard simultaneous peptide-resin cleavage and removal of the acid-labile side-chain protecting groups affords the crude peptides containing fluorosulfated tyrosine. Basic ethylene glycol, serving both as solvent and reactant, transforms the fluorosulfated tyrosine peptides into sulfotyrosine peptides in high yield.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Wentao
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Suhua
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.|The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Yoon
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA. sharples@scripps.edu.|The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA. sharples@scripps.edu.
authors.forename: K Barry
authors.initials: KB
authors.lastname: Sharpless
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, 92037, USA. jkelly@scripps.edu.|Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA. jkelly@scripps.edu.|The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA. jkelly@scripps.edu.
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Kelly
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; C005662:tyrosine O-sulfate; D014443:Tyrosine
keywords: SuFEx; click chemistry; peptides; solid-phase synthesis; sulfotyrosine