title: Radical arylation of tyrosine and its application in the synthesis of a highly selective neurotensin receptor 2 ligand.
abstract: A small library of Fmoc-protected 3-arylated tyrosines was created by radical arylation. The new building blocks were successfully applied in the synthesis of two novel neurotensin receptor ligands. Both isomers showed high affinity for the human NTS2 receptor with K(i) values in the nanomolar range. Interestingly, subtype selectivity strongly depends on the configuration of the peptide in position 11. Isomer (11R)-3 displayed an excellent preference for NTS2 compared to NTS1.
authors.affiliation: Department für Chemie und Pharmazie, Pharmazeutische Chemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Pratsch
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Unfried
authors.forename: Jürgen
authors.initials: J
authors.lastname: Einsiedel
authors.forename: Manuel
authors.initials: M
authors.lastname: Plomer
authors.forename: Harald
authors.initials: H
authors.lastname: Hübner
authors.forename: Peter
authors.initials: P
authors.lastname: Gmeiner
authors.forename: Markus R
authors.initials: MR
authors.lastname: Heinrich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005449:Fluorenes / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D008024:Ligands; D009496:Neurotensin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D018028:Receptors, Neurotensin / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry*
chemical_list: C496789:9-fluorenylmethoxycarbonyl; D005449:Fluorenes; D005609:Free Radicals; D008024:Ligands; C490985:NTSR2 protein, human; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D014443:Tyrosine