Red-fluorescent argininamide-type NPY Y1 receptor antagonists as pharmacological tools

被引：34

作者：

Keller, Max ^{[1
]}

Erdmann, Daniela ^{[1
]}

Pop, Nathalie ^{[1
]}

Pluym, Nikola ^{[1
]}

Teng, Shangjun ^{[1
]}

Bernhardt, Guenther ^{[1
]}

Buschauer, Armin ^{[1
]}

机构：

[1] Univ Regensburg, Inst Pharm, D-93040 Regensburg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 09期

关键词：

NPY Y-1 receptor; Fluorescent ligands; Y1R binding; Y1R antagonism; Argininamide derivatives; Confocal microscopy; Flow cytometry; NEUROPEPTIDE-Y RECEPTORS; SUBTYPE SELECTIVITY; CHAMELEON LABELS; FLOW-CYTOMETRY; HIGHLY POTENT; EXPRESSION; CANCER; AFFINITY; TUMORS; CELLS;

D O I：

10.1016/j.bmc.2011.03.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fluorescently labelled NPY Y-1 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 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 Y1R probe, which was also successfully applied in flow cytometry. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2859 / 2878

页数：20

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