1-Benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diols as novel affinity and photoaffinity probes for β-adrenoceptor subtypes

Victor I. Nikulin, Igor M. Rakov, Joseph E. De Los Angeles, Ratna C. Mehta, Lene'Sheya Y. Boyd, Dennis R. Feller, Duane Miller

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Trimetoquinol (TMQ, 1) is a potent non-selective β-adrenoceptor (β-AR) agonist possessing a tetrahydroisoquinoline (THI) structure. The binding site for 1-trimethoxybenzyl group of 1, which distinguishes it from classical catecholamines, is unknown. Affinity and photoaffinity labeled compounds are good tools to determine the exact interaction between a ligand and a specific amino acid(s) in a receptor. In this study, we designed and synthesized a series of affinity 6, 12, 18, and photoaffinity 24, 29 labeled analogues of TMQ. All of these compounds were full agonists and demonstrated an equal or greater binding affinity and functional activity as compared to TMQ on β1-, β2-, and β3-AR. Washout experiments on Chinese hamster ovary (CHO) cells expressing hu β2-AR were helpful in identifying the isothiocyanate 18 and the azide 24 as very effective affinity and photoaffinity labels at this receptor subtype.

Original languageEnglish (US)
Pages (from-to)1684-1697
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number6
DOIs
StatePublished - Mar 15 2006

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Tretoquinol
Photoaffinity Labels
Affinity Labels
Tetrahydroisoquinolines
Azides
Cricetulus
Adrenergic Receptors
Catecholamines
Ovary
Binding Sites
Cells
Ligands
Amino Acids
Experiments
1,2,3,4-tetrahydro-1-(phenylmethyl)isoquinoline
isothiocyanic acid

All Science Journal Classification (ASJC) codes

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

Cite this

1-Benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diols as novel affinity and photoaffinity probes for β-adrenoceptor subtypes. / Nikulin, Victor I.; Rakov, Igor M.; De Los Angeles, Joseph E.; Mehta, Ratna C.; Boyd, Lene'Sheya Y.; Feller, Dennis R.; Miller, Duane.

In: Bioorganic and Medicinal Chemistry, Vol. 14, No. 6, 15.03.2006, p. 1684-1697.

Research output: Contribution to journalArticle

Nikulin, Victor I. ; Rakov, Igor M. ; De Los Angeles, Joseph E. ; Mehta, Ratna C. ; Boyd, Lene'Sheya Y. ; Feller, Dennis R. ; Miller, Duane. / 1-Benzyl-1,2,3,4-tetrahydroisoquinoline-6,7-diols as novel affinity and photoaffinity probes for β-adrenoceptor subtypes. In: Bioorganic and Medicinal Chemistry. 2006 ; Vol. 14, No. 6. pp. 1684-1697.
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