title: Design and synthesis of an Fmoc-SPPS-compatible amino acid building block mimicking the transition state of phosphohistidine phosphatase.
abstract: The synthesis of a sulfonamide-based transition-state (TS) analogue of enzymatic phosphohistidine dephosphorylation as an amino acid building block is presented, together with the proof-of-concept of its incorporation into peptides. Key features include final global acidolytic protective group removal as well as full compatibility with standard Fmoc solid-phase peptide synthesis (SPPS). The peptides are designed as inhibitors of phosphohistidine phosphatase and as a pull-down probe for identification of phosphohistidine phosphatases, respectively.
authors.affiliation: Department of Chemical Biology, Max Planck Institute for Molecular Physiology, Otto-Hahn Strasse 11, Dortmund D-44227, Germany.
authors.forename: Martijn F
authors.initials: MF
authors.lastname: Eerland
authors.forename: Christian
authors.initials: C
authors.lastname: Hedberg
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D005449:Fluorenes / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D060327:Solid-Phase Synthesis Techniques; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D013449:Sulfonamides; C504019:PHPT1 protein, human; D010744:Phosphoric Monoester Hydrolases