title: A new approach to phosphoserine, phosphothreonine and phosphotyrosine synthons and to thiophospho analogs. Stepwise synthesis of mono- and multiphosphorylated phosphopeptides related to src-protein kinase.
abstract: Several phosphoserine, phosphothreonine and phosphotyrosine synthons suitable for the stepwise synthesis of phosphopeptides were prepared. Treatment of methylthiomethyl (MTM) esters of either Z-, Boc-, Allocserine and threonine with phosphochloridate in pyridine followed by MgBr2 cleavage of MTM in diethyl ether afforded the title compounds in good yield. Thiophosphoserine and phosphotyrosine synthons were also obtained by the phosphoramidite method using di-(2,2,2-trichloroethyl)-N,N-diisopropylphosphoramidite and MCPBA as oxidizing reagent. Trichloroethyl proved valuable as phosphate protecting group especially in phosphotyrosine derivatives owing to its stability in acidic conditions. These synthons were involved in the liquid-phase synthesis of several phospho and/or thiophosphopeptides related to either src-protein kinase or rat liver pyruvate kinase.
authors.affiliation: Laboratory of Bioorganic Chemistry, University of Avignon, France.
authors.forename: N
authors.initials: N
authors.lastname: Mora
authors.forename: J M
authors.initials: JM
authors.lastname: Lacombe
authors.forename: A A
authors.initials: AA
authors.lastname: Pavia
mesh_terms: D000595:Amino Acid Sequence; D000081247:CSK Tyrosine-Protein Kinase; D008969:Molecular Sequence Data; D063086:Organothiophosphates / Q000138:chemical synthesis*; D010748:Phosphopeptides / Q000138:chemical synthesis*; D010766:Phosphorylation; D010768:Phosphoserine / Q000737:chemistry*; D010769:Phosphothreonine / Q000737:chemistry*; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000138:chemical synthesis*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry; D019061:src-Family Kinases
chemical_list: D063086:Organothiophosphates; D010748:Phosphopeptides; D010769:Phosphothreonine; D010768:Phosphoserine; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases