Cathepsin K is a cysteine peptidase, that is considered a target for the treatment of osteoporosis. One way to inhibit this enzyme is targeting allosteric sites. Several allosteric inhibitors of cathepsin K are known. In the synthesis of inhibitor NSC94914, 2-([1,1’-biphenyl]-2-ylmethyl)malonic acid, I firstly undertook the nucleophilic substitution. Initially, I deprotonated dibenzyl malonate with NaH and later reacted it with 2-phenylbenzyl bromide. After purification by column chromatography, the obtained dibenzyl ester was catalytically hydrogenated to get the desired product NSC94914. Using enzyme assays with the fluorogenic substrate Z-FR-AMC, I characterized NSC94914, determined the method of inhibition and the binding affinity. It has been shown, that this compound causes a complete inhibition. The result contradicts the published research findings, which could be due to the impure compound NSC94914 or lost enzyme activity during testing.
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