title: Red-fluorescent argininamide-type NPY Y1 receptor antagonists as pharmacological tools.
abstract: Fluorescently labelled NPY Y(1) receptor (Y(1)R) ligands were synthesized by connecting pyrylium and cyanine dyes with the argininamide-type Y(1)R antagonist core structure by linkers, covering a wide variety in length and chemical nature, attached to the guanidine group. The most promising fluorescent probes had Y(1)R affinities (radioligand binding) and antagonistic activities (calcium assay) in the one- to two-digit nanomolar range. These compounds turned out to be stable under assay conditions and to be appropriate for the detection of Y(1)Rs by confocal microscopy in live cells. To improve the signal-to-noise ratio by shifting the emission into the near infrared, a new benzothiazolium-type fluorescent cyanine dye (UR-DE99) was synthesized and attached to the parent antagonist via a carbamoyl linker yielding UR-MK131, a highly potent fluorescent Y(1)R probe, which was also successfully applied in flow cytometry.
authors.affiliation: Institut für Pharmazie, Universität Regensburg, D-93040 Regensburg, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Keller
authors.forename: Daniela
authors.initials: D
authors.lastname: Erdmann
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pop
authors.forename: Nikola
authors.initials: N
authors.lastname: Pluym
authors.forename: Shangjun
authors.initials: S
authors.lastname: Teng
authors.forename: Günther
authors.initials: G
authors.lastname: Bernhardt
authors.forename: Armin
authors.initials: A
authors.lastname: Buschauer
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D052160:Benzothiazoles / Q000737:chemistry; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D011485:Protein Binding; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D005456:Fluorescent Dyes; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C069339:argininamide; D001120:Arginine