Bodilisant-a novel fluorescent, highly affine histamine h3 receptor ligand

Miriam Tomasch; J Stephan Schwed; Alexander Paulke; Holger Stark

doi:10.1021/ml300383n

Bodilisant-a novel fluorescent, highly affine histamine h3 receptor ligand

ACS Med Chem Lett. 2012 Dec 12;4(2):269-73. doi: 10.1021/ml300383n. eCollection 2013 Feb 14.

Authors

Miriam Tomasch¹, J Stephan Schwed¹, Alexander Paulke², Holger Stark¹

Affiliations

¹ Goethe University , Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany.
² Goethe University , Kennedyallee 104, 60596 Frankfurt am Main, Germany.

Abstract

A piperidine-based lead structure for the human histamine H3 receptor (hH3R) was coupled with the BODIPY fluorophore and resulted in a strong green fluorescent (quantum yield, 0.92) hH3R ligand with affinity in the nanomolar concentration range (K i hH3R = 6.51 ± 3.31 nM), named Bodilisant. Screening for affinities at histamine and dopamine receptor subtypes showed high hH3R preference. Bodilisant was used for visualization of hH3R in hH3R overexpressing HEK-293 cells with fluorescence confocal laser scanning microscopy. In addition, in native human brain tissues, Bodilisant showed clear and displaceable images of labeled hH3R.

Keywords: BODIPY; GPCR; H3 receptor; HEK-293 cells; displacement; fluorescence confocal laser scanning microscopy; histamine; nonimidazole derivative; pharmacological tool; tissue labeling.