Bitopic ligands: all-in-one orthosteric and allosteric
نویسندگان
چکیده
Natural ligands of G-protein-coupled receptors interact with the orthosteric ligand binding site, as do most of the classical synthetic ligands. The discovery of ligands targeting different, allosteric binding sites considerably expanded the repertoire of G-protein-coupled receptor ligands. More recently, bitopic ligands have been described that target both orthosteric and allosteric sites at the same time.
منابع مشابه
Exploration of the orthosteric/allosteric interface in human M1 muscarinic receptors by bitopic fluorescent ligands.
Bitopic binding properties apply to a variety of muscarinic compounds that span and simultaneously bind to both the orthosteric and allosteric receptor sites. We provide evidence that fluorescent pirenzepine derivatives, with the M1 antagonist fused to the boron-dipyrromethene [Bodipy (558/568)] fluorophore via spacers of varying lengths, exhibit orthosteric/allosteric binding properties at mus...
متن کاملMol #85670 1 Exploration of the Orthosteric/allosteric Interface in Human M1 Muscarinic Receptors by Bitopic Fluorescent Ligands
Bitopic binding properties apply to a variety of muscarinic compounds that span and simultaneously bind to both the orthosteric and allosteric receptor sites. We provide evidence that fluorescent pirenzepine derivatives, with the M1 antagonist fused to the Bodipy [558/568] fluorophore via spacers of varying lengths, exhibit orthosteric/allosteric binding properties at muscarinic M1 receptors. T...
متن کاملMicrosoft Word - 90462598-file00
Bitopic binding properties apply to a variety of muscarinic compounds that span and simultaneously bind to both the orthosteric and allosteric receptor sites. We provide evidence that fluorescent pirenzepine derivatives, with the M1 antagonist fused to the Bodipy [558/568] fluorophore via spacers of varying lengths, exhibit orthosteric/allosteric binding properties at muscarinic M1 receptors. T...
متن کاملA new mechanism of allostery in a G protein-coupled receptor dimer
SB269652 is to our knowledge the first drug-like allosteric modulator of the dopamine D2 receptor (D2R), but it contains structural features associated with orthosteric D2R antagonists. Using a functional complementation system to control the identity of individual protomers within a dimeric D2R complex, we converted the pharmacology of the interaction between SB269652 and dopamine from alloste...
متن کاملBinding of N-methylscopolamine to the extracellular domain of muscarinic acetylcholine receptors
Interaction of orthosteric ligands with extracellular domain was described at several aminergic G protein-coupled receptors, including muscarinic acetylcholine receptors. The orthosteric antagonists quinuclidinyl benzilate (QNB) and N-methylscopolamine (NMS) bind to the binding pocket of the muscarinic acetylcholine receptor formed by transmembrane α-helices. We show that high concentrations of...
متن کامل