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Designing Caspase-1 Kinase Inhibitors to Control Acute Inflammation of Orthodontic Appliances
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1  Department of Chemistry, The Richard Stockton College of New Jersey, Galloway NJ 08205-9441.

Abstract: Orthodontics is a branch of dentistry that uses tensile force from intraoral or extraoral orthodontic appliances to resolve dental malocclusions. The use of tensile force seeks to remodel periodontal ligament and alveolar bone however this process initiates acute inflammation and necrotic conditions in the periodontium. This acute inflammation arises through multiple mechanisms including that of the inflammasome conversion of pro- interleukin 1β (IL-1β) to the active form.1,2 Inhibition of one major protein found in the inflammasome, Caspase-1, has been found to block the activation of IL-1β thereby blocking the acute inflammation initiated by appliance tightening.3-5 This research sought to understand binding interaction of pharmaceuticals to the protein kinase functionality of the Caspase-1. 22 crystal structures of the kinase of the Caspase-1 protein were docked using IGEMDock to FDA, Alkaloids, Lactams, Lactones, Flavinoids, Sulfanilamide, Cyclic Imides, and NSAIDs drugs to determine structural correlation for the most effective binders. Structural similarities were determined with IGEMDock and vROCS and partition coefficient was determined using DRAGON program. This data found a cluster of approximately 10 drugs to preferentially bind to the Caspase-1 kinase for use as targeted anti-inflammatory treatments. This work will be used in the engineering of improved Caspase-1 kinase inhibitors.
Keywords: Caspase-1, IL-1 beta, Inflammation