title: Use of the Sonogashira coupling reaction for the "two-step" labeling of phenylalanine peptide side chains with organometallic compounds.
abstract: The Pd-catalyzed Sonogashira coupling of ferrocene alkyne derivatives as metal probes to iodophenylalanine containing peptides is described. 4-Iodophenylalanine was incorporated into dipeptides and the neuropeptide [Leu5]-enkephalin (Enk) by solid phase peptide synthesis, thereby creating a functional group suitable for the Sonogashira coupling. The reaction with two different ferrocene alkynes resulted in the corresponding ferrocene-labeled derivatives, which were obtained in good yield and purity. All new compounds were comprehensively characterized, including elemental analysis, 1D and 2D NMR, EI-, FAB- or ESI-MS, IR and UV-vis spectroscopy, and electrochemistry of the ferrocene label. Unlike well-established conjugation methods for peptide side chains such as lysine and cystein, the phenyl group in Phe is not readily available for derivatization. This work presents a versatile procedure for the regioselective introduction of an organometallic label into biologically relevant peptides as exemplified for enkephalin.
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hoffmanns
authors.forename: Nils
authors.initials: N
authors.lastname: Metzler-Nolte
mesh_terms: D004563:Electrochemistry; D004745:Enkephalins / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry*; D000075163:Metallocenes; D010455:Peptides / Q000138:chemical synthesis; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D004745:Enkephalins; D005296:Ferrous Compounds; D000075163:Metallocenes; D010455:Peptides; D010649:Phenylalanine; C049181:4-iodophenylalanine; C004998:ferrocene