Receptor–Ligand Interaction Measured by Inductively Coupled Plasma Mass Spectrometry and Selenium Labeling

Abstract

In the search for an alternative strategy to the radioactivity measurement conventionally performed to probe receptor−ligand interactions in pharmacological assays, we demonstrated that selenium labeling of the studied ligand combined with elemental mass spectrometry was as efficient and robust as the reference method but devoid of its environmental and health hazards. The proof-of-concept was illustrated on two GPCR receptors, vasopressin (V 1A ) and cholecystokinin B (CCK-B), involving peptides as endogenous ligands. We proposed several methodologies to produce selenium-labeled ligands according to peptide sequences along with binding affinity constraints. A selection of selenopeptides that kept high affinities toward the targeted receptor were engaged in saturation and competitive binding experiments with subsequent sensitive RP-LC-ICP-MS measurements. Experimental values of affinity constant (K i ) were perfectly correlated to literature data, illustrating the general great potency of replacing radioactive iodine by selenium for ligand labeling to further undergo unaffected pharmacology experiments efficiently monitored by elemental mass spectrometry.

Recent Progress in Cyclic Aryliodonium Chemistry: Syntheses and Applications

“…Their work illustrates how HCIs can be efficiently utilized to access complex building blocks. Considering the essential functions of selenium or silicon-containing frameworks in drugs − or optoelectronic materials, − concise synthetic routes to these scaffolds are receiving much attention. − In 2017, Xu and co-workers disclosed copper-catalyzed dual arylations between cyclic diaryliodoniums 91 and Se, potassium thioacetate (AcSK), or dichlorodimethylsilane for construction of triselenasumanene, chalcogenasumanenes, and silicon-containing heterosumanene 92 , which may pose considerable synthetic challenges of preparation by conventional approaches (Scheme B) . It is noteworthy that this protocol would inspire the study of iodine-doping to the aromatic frameworks for the synthesis of novel curved and planar π-extended materials, such as nanoloops, buckybowls, and nanographenes.…”

Regioselective Radical Cascade Cyclizations of Alkyne-Tethered Cyclohexadienones with Chalcogenides under Visible-Light Catalysis

“…The title compound was prepared according to the general procedure as described above (i) in a 78% (84 mg) yield; it was purified by column chromatography (20% EtOAc/hexane; R f = 0.2) to afford 4c as a white solid (mp: 188−193 °C). 5R,5,6,benzoate (4d). The title compound was prepared according to the general procedure as described above (i) in a 93% (95 mg) yield; it was purified by column chromatography (20% EtOAc/ hexane; R f = 0.2) to afford 4d as a white solid (mp:193−198 °C).…”

“…Organochalcogen compounds, particularly containing sulfonyl (R 1 SO 2 −) and seleno (R 2 Se−) groups, are highly versatile functional groups that are widely present in natural products and pharmaceuticals and play a substantial role in organic synthesis (nucleophiles, electrophiles, ligands, and catalysts), biochemistry, medicinal chemistry, and materials science . Additionally, molecules containing selenium and sulfone have been widely used in organic synthesis .…”

Discussions of Fluorescence in Selenium Chemistry: Recently Reported Probes, Particles, and a Clearer Biological Knowledge

“…There is a discussion of molecular tags which contain an atom of selenium. Selenium tags are those of an AVP ligand nature; also HO-Phpa-LVA ligand and the CCK-4 ligand is also known [37].…”