Small-molecule drug screening platform employing DNA aptamers for the identification of new drugs for osteoporosis

Category: *Precision Health & Smart Medical

Exhibitor: CHANG JUNG CHRISTIAN UNIVERSITY

Booth No: N516

Characteristic

Sclerostin, a secreted glycoprotein that inhibits bone formation by antagonizing the Wnt/β-catenin signaling pathway, is considered a new target for the treatment of osteoporosis. Current strategies to stimulate bone formation by sclerostin inhibition are mostly focused on the development of antibody drugs, but the long-term risk of such treatment remains to be assessed. The drug screening platform was set up with a nickel-coated 96-well black plate pre-blocked with bovine serum albumin, to which histidine-tagged recombinant human sclerostin protein (rhSOST) was immobilized. In each well immobilized with rhSOST, FAM-labeled sclerostin-specific aptamer and a selected small-molecule drug were added, followed by reaction at room temperature for 1 h. After rinsing to remove excess aptamers and chemicals, the fluorescence intensity of each well was determined by a microplate fluorometer at Ex485 nm/Em520 nm. Compounds with binding affinity higher than the aptamer may associate with the target protein, thus displacing the fluorescence-labeled aptamer. Potential inhibitors of sclerostin can then be identified by a significant decrease in fluorescence compared to the aptamer-only control. This technology facilitates drug repurposing, one of the initiatives of National Center for Advancing Translational Sciences (NCATS), and accelerates the progress of drug discovery for osteoporosis. The platform can be employed in the drug screening of other target proteins with target-specific aptamers, and integrated into a high-throughput drug screening workflow to reduce the cost of identifying new drugs.