Binding Mode Based Chemical Screening Method Utilizing D-Ala-D-Ala Silica Gel Facilitating the Discovery of Overlooked Binding Affinity and Antibacterial Activity

Abstract

In this work, a new chemical screening method has been established, namely binding mode-based chemical screening (BMBC), using D-Ala-D-Ala-functionalized silica gel. This method was inspired by the binding mode of vancomycin to the bacterial cell wall and enables the discovery of new natural compounds with antibacterial activity. In this study, we aimed to uncover overlooked binding affinity and antibacterial activity of compounds from our in-house natural product library (the Ōmura Natural Compound Library) and estimated the binding constants of hit compounds to empower BMBC method to show the utility and validity. Ultimately, we discovered the overlooked binding affinity and antibacteria activity of ascofuranone and cercosporin. Particularly, cercosporin demonstrated remarkable antibacterial activity against Staphylococcus epidermidis clinical isolates.

Keywords: D‐Ala‐D‐Ala silica gel; antibiotics; chemical screening; the Ōmura natural product library.