An efficient biosensor based on the synergistic catalysis of Helicobacter pylori urease b subunit and nanoplatinum for urease inhibitors screening and antagonistic mechanism analyzing

Abstract

Helicobacter pylori (H. pylori) is the main non-genetic factor leading to gastric cancer. Due to the important role of urease produced by H. pylori in its initial colonization, survival, and infection, the activity inhibition of urease has been proven to be a promising therapeutic strategy for H. pylori infection. Therefore, the screening of effective urease inhibitors has become an important direction for the development of new therapeutic drugs. In this study, a novel biosensor for rapid screening of H. pylori urease inhibitors was constructed based on glassy carbon electrode (GCE) modified by heterologously expressed H. pylori 26695 urease b subunit (HPUb), Pt nanoparticles, and nanoporous gold (NPG). Five inhibitors were successfully screened for HPUb using the proposed biosensor (HPUb/Pt/NPG/GCE). The inhibition constants calculated according to the established mathematical model indicated that the inhibitory intensity order of these inhibitors was methylurea > acetamide > formamide > acetohydroxamic acid > hydroxyurea. Combining the inhibition constant of urease inhibitors with the molecular binding mechanism of the urease inhibitor and HPUb, it can be inferred that the non-polar long-chain modification of one of the primary amino groups based on the molecular structure of urea is a promising direction for the development of high-efficiency urease inhibitors. The elucidation of this mechanism will provide a theoretical foundation and new ideas for the design of competitive urease inhibitors based on urea structure and the development of new anti H. pylori drugs.