Improved Surface Display of Human Hyal1 and Identification of Testosterone Propionate and Chicoric Acid as New Inhibitors.

摘要: Degradation of high molecular weight hyaluronic acid (HA) in humans is mainly catalyzed by hyaluronidase Hyal1. This enzyme involved many pathophysiological processes and therefore appears an interesting target for drug discovery. Until now, only a few inhibitors human Hyal1 are known due to obstacles obtaining active enzymes inhibitor screening. The aim the present work was provide convenient activity assay show its feasibility identification new inhibitors. By autodisplay, Escherichia coli F470 can on surface. In this study, inducible expression cell surface E. under control rhamnose-dependent promoter (Prha) performed optimized. Enzyme per single increased factor 100 compared constitutive display, as described before. An 6.8 × 10−4 mU obtained optimal reaction conditions. modified assay, two were identified. Chicoric acid, natural compound belonging phenylpropanoids, showed IC50 value 171 µM. steroid derivative testosterone propionate 124 ± 1.1 Both values same order magnitude glycyrrhizic (177 µM), one best so far. conclusion, we established identified with method.