Synthesis and pharmacological characterization of novel fluorescent histamine H2-receptor ligands derived from aminopotentidine

Sheng Xue Xie, Georgiana Petrache, Erich Schneider, Qi Zhuang Ye, Günther Bernhardt, Roland Seifert, Armin Buschauer

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

In an effort to develop a non-radioactive alternative to the [3H]tiotidine and [125I]iodoaminopotentidine binding assays for the histamine H2-receptor (H2R), primary amines related to aminopotentidine were prepared and coupled with the succinimidyl esters of the bulky fluorescent dyes S0536 and BODIPY® 650/665-X. The primary amines exhibited different degrees of antagonistic potency at the human and guinea pig H2R. Surprisingly, one compound (5) coupled to the cyanine dye S0536 acted as potent partial agonist/antagonist at the H2R (KB ∼ 50 nM; EC50 ∼ 100-150 nM). Compounds coupled to the BODIPY dye exhibited moderately high H2R-affinity, too. Thus, the H2R accommodates bulky fluorophores, probably through interaction with extracellular receptor domains. The compounds presented herein provide a starting point for the optimization of fluorescent H2R ligands with respect to affinity and fluorescence as valuable tools to analyze the molecular mechanisms of H2R activation.

Original languageEnglish (US)
Pages (from-to)3886-3890
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number15
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

Keywords

  • BODIPY
  • Cyanine
  • Fluorescent probes
  • GTPase assay
  • Histamine H-receptor agonist

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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