title: Fluorescent Human EP3 Receptor Antagonists.
abstract: Exchange of the lipophilc part of ortho-substituted cinnamic acid lead structures with different small molecule fluorophoric moieties via a dimethylene spacer resulted in hEP3R ligands with affinities in the nanomolar concentration range. Synthesized compounds emit fluorescence in the blue, green, and red range of light and have been tested concerning their potential as a pharmacological tool. hEP3Rs were visualized by confocal laser scanning microscopy on HT-29 cells, on murine kidney tissues, and on human brain tissues and functionally were characterized as antagonists on human platelets. Inhibition of PGE2 and collagen-induced platelet aggregation was measured after preincubation with novel hEP3R ligands. The pyryllium-labeled ligand 8 has been shown as one of the most promising structures, displaying a useful fluorescence and highly affine hEP3R antagonists.
authors.affiliation: Goethe University , Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Tomasch
authors.affiliation: Goethe University , Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany.
authors.forename: J Stephan
authors.initials: JS
authors.lastname: Schwed
authors.affiliation: Goethe University , Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Kuczka
authors.affiliation: Goethe University , Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Meyer Dos Santos
authors.affiliation: Goethe University , Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
authors.affiliation: Goethe University , Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Nüsing
authors.affiliation: Goethe University , Kennedyallee 104, 60596 Frankfurt am Main, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Paulke
authors.affiliation: Goethe University , Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
keywords: EP3 receptor; GPCR; cinnamic acid derivatives; confocal laser scanning microscopy; fluorescence; human brain; imaging; murine kidney; platelet aggregation; prostanoid