title: Bis(arylmethyl)-substituted unsymmetrical phosphites for the synthesis of lipidated peptides via Staudinger-phosphite reactions.
abstract: With this study we introduce new unsymmetrical phosphites to obtain lipidated peptide-conjugates starting from easily accessible azide-modified amino acid or peptide precursors. For this purpose, we investigated which substituents at alkyl phosphites lead to the highest formation of mono-alkylated phosphoramidate peptides. We found that phosphites containing one alkyl-chain and two picolyl or benzyl-substituents delivered alkyl phosphoramidate-conjugates in high yields, which also allowed a chemoselective lipidation of an unprotected azido polypeptide. Finally, monolipidated phosphoramidate peptides obtained by the unsymmetrical Staudinger phosphite reaction led to the formation of micelle-like structures and cellular uptake.
authors.affiliation: Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin, Germany. hackenbe@fmp-berlin.de.
authors.forename: N
authors.initials: N
authors.lastname: Nischan
authors.forename: M-A
authors.initials: MA
authors.lastname: Kasper
authors.forename: T
authors.initials: T
authors.lastname: Mathew
authors.forename: C P R
authors.initials: CP
authors.lastname: Hackenberger
mesh_terms: D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D017905:Phosphites / Q000737:chemistry*
chemical_list: D010455:Peptides; D017905:Phosphites