Add time:09/07/2019         Source:sciencedirect.com

Fluorescently labelled NPY Y1 receptor (Y1R) ligands were synthesized by connecting pyrylium and cyanine dyes with the argininamide-type Y1R 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 Y1R 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 Y1Rs 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 Y1R probe, which was also successfully applied in flow cytometry.

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