Ligands for Glaucoma-Associated Myocilin Discovered by a Generic Binding Assay was written by Orwig, Susan D.;Chi, Pamela V.;Du, Yuhong;Hill, Shannon E.;Cavitt, Marchello A.;Suntharalingam, Amrithaa;Turnage, Katherine C.;Dickey, Chad A.;France, Stefan;Fu, Haian;Lieberman, Raquel L.. And the article was included in ACS Chemical Biology in 2014.Quality Control of 3,5-Dibromo-4-methoxybenzaldehyde This article mentions the following:
Mutations in the olfactomedin domain of myocilin (myoc-OLF) are the strongest link to inherited primary open angle glaucoma. In this recently identified protein misfolding disorder, aggregation-prone disease variants of myocilin hasten glaucoma-associated elevation of intraocular pressure, leading to vision loss. Despite its well-documented pathogenic role, myocilin remains a domain of unknown structure or function. Here we report the first small-mol. ligands that bind to the native state of myoc-OLF. To discover these mols., we designed a general label-free, mix-and-measure, high throughput chem. assay for restabilization (CARS), which is likely readily adaptable to discover ligands for other proteins. Of the 14 hit mols. identified from screening myoc-OLF against the Sigma-Aldrich Library of Pharmacol. Active Compounds using CARS, surface plasmon resonance binding studies reveal three are stoichiometric ligand scaffolds with low micromolar affinity. Two compounds, GW5074 and apigenin, inhibit myoc-OLF amyloid formation in vitro. Structure-activity relationship-based soluble derivatives reduce aggregation in vitro as well as enhance secretion of full-length mutant myocilin in a cell culture model. Our compounds set the stage for a new chem. probe approach to clarify the biol. function of wild-type myocilin and represent lead therapeutic compounds for diminishing intracellular sequestration of toxic mutant myocilin. In the experiment, the researchers used many compounds, for example, 3,5-Dibromo-4-methoxybenzaldehyde (cas: 108940-96-1Quality Control of 3,5-Dibromo-4-methoxybenzaldehyde).
3,5-Dibromo-4-methoxybenzaldehyde (cas: 108940-96-1) belongs to organobromine compounds. Most of the natural organobromine compounds are produced by marine organisms, and several brominated metabolites with antibacterial, antitumor, antiviral, and antifungal activity have been isolated from seaweed, sponges, corals, molluscs, and others. In the pharmaceutical industry organo bromine derivatives are used as sedatives, vasodilators, antiseptic agents, and anticancer agents.Quality Control of 3,5-Dibromo-4-methoxybenzaldehyde
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bromide – Wiktionary