A photoreactive probe that differentiates the binding sites of noncompetitive GABA receptor antagonists

Probing Structural Features and Binding Mode of 3-Arylpyrimidin-2,4-diones within Housefly γ-Aminobutyric Acid (GABA) Receptor

“…Although the amino acids V5′ and L9′ of Rdl subunit are indirectly involved in the binding of APDs, the amino acids at 5′ and 9′ positions in TM2 region are also two potential sites responsible for the binding of NCAs, while the fipronil-related NCAs [10,12] are in hydrophobic contact with I5′ and L9′ of β 3 subunit. Whereas, compared with fipronil [2], S17′ residues within the channel does not exist in the interaction of APDs. In summary, structurally different classes of NCAs bind to two identical sites and two potential sites in different or overlapping orientations within the channel pore of the GABA receptor, except for a few NCAs with multiple sites.…”

“…However, some other evidences also suggested that the structurally diverse NCAs might have distinct binding modes in GABA receptor [2,17,18]. For instance, fipronil might bind to the TM3 while picrotoxinin and dieldrin bind to the TM2 region of GABA receptor [2].…”

“…However, some other evidences also suggested that the structurally diverse NCAs might have distinct binding modes in GABA receptor [2,17,18]. For instance, fipronil might bind to the TM3 while picrotoxinin and dieldrin bind to the TM2 region of GABA receptor [2]. However, it still remains ambiguous whether all NCAs with diverse structures interact at the same or an overlapping site, or multiple sites within the channel pore [16,19].…”

Deoxynucleoside triphosphates bearing histamine, carboxylic acid, and hydroxyl residues – synthesis and biochemical characterization

“…Indeed, commercially available 5-iodo-2′-deoxycytidine 15 was converted into the ester functionalized nucleoside 16 in good yield (90%) using a Sonogashira cross-coupling reaction with 4-pentynoic acid methyl ester. 80 The free 5′-hydroxyl residue of…”

Oscillatory carbonylation using alkyne-functionalised poly(ethylene glycol)

“…PEGA (2000 and 5000 Da), and methyl 4-pentynoate (4MP, a 'monomeric' analogue of PEGA) were synthesised from commercially available starting materials according to literature procedures. [17][18][19] For each oscillatory run a catalyst solution consisting of palladium(II) iodide and potassium iodide in methanol was equilibrated to 20 1C and a baseline pH value established. Solutions were then purged with carbon monoxide and air for 15 min and treated with methanolic solutions of PEGA.…”