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ConoServer (http://www.conoserver.org) is a database specializing in the sequences and structures of conopeptides, which are toxins expressed by marine cone snails. Cone snails are carnivorous gastropods, which hunt their prey using a cocktail of toxins that potently subvert nervous system function. The ability of these toxins to specifically target(More)
α-Conotoxin Vc1.1 specifically and potently inhibits the nicotinic acetylcholine receptor subtype α9α10 (α9α10 nAChR) and is a potential novel treatment for neuropathic pain. Here, we used a combination of computational modeling and electrophysiology experiments to determine the Vc1.1 binding site on the α9α10 nAChR. Interactions of Vc1.1 with two probable(More)
α-Conotoxins potently and specifically inhibit isoforms of nicotinic acetylcholine receptors (nAChRs) and are used as molecular probes and as drugs or drug leads. Interactions occurring during binding and unbinding events are linked to binding kinetics, and knowledge of these interactions could help in the development of α-conotoxins as drugs. Here, the(More)
A series of 2-pyridinyl-3-substituted-4(3H)-quinazolinones were synthesized, and their anti-influenza A virus activities were determined using the cytopathic effect inhibition assay. Most of the compounds were potent with IC50 values ranging from 51.6 to 93.0 μm, which are better than that of the currently marketed drug ribavirin. The molecular mechanisms(More)
α-Conotoxins potently inhibit isoforms of nicotinic acetylcholine receptors (nAChRs), which are essential for neuronal and neuromuscular transmission. They are also used as neurochemical tools to study nAChR physiology and are being evaluated as drug leads to treat various neuronal disorders. A number of experimental studies have been performed to(More)
Nicotinic acetylcholine receptors (nAChRs) are drug targets for neuronal disorders and diseases. Partial agonists for nAChRs are currently being developed as drugs for the treatment of neurological diseases for their relative safety originated from reduced excessive stimulation. In the current study, molecular docking, molecular dynamics simulations and(More)
The human glycine receptor (hGlyR) is an anion-permeable ligand-gated channel that is part of a larger superfamily of receptors called the Cys-loop family. hGlyRs are particularly amenable to single-channel recordings, thus making them a model experimental system for understanding the Cys-loop receptor family in general. Understanding the relationship(More)
Glycine receptors (GlyR) belong to the pentameric ligand-gated ion channel (pLGIC) superfamily and mediate fast inhibitory transmission in the vertebrate CNS. Disruption of glycinergic transmission by inherited mutations produces startle disease in man. Many startle mutations are in GlyRs and provide useful clues to the function of the channel domains.(More)
Oleanolic acid (OA) is a well-known pentacyclic triterpenoid compound, which has been used as a dietary supplement and is supplied as an over-the-counter drug for the treatment of human liver diseases. These are reasons for the low bioavailability of OA which have restricted its wider application. In this study, two OA prodrugs (1,3-cyclic propanyl(More)
α-Conotoxins, a class of short and disulfide rich peptide toxins, specifically and potently block nicotinic acetylcholine receptors (nAChRs). In this study umbrella sampling was performed to study the unbinding pathways and potential of mean force (PMF) of α-conotoxin ImI and PNIA(A10L,D14K). Our results suggest that (i) the unbinding pathways of ImI and(More)