Kimishima Aoi, Suzuki Yuki, Kosaka Shohei, Honsho Masako, Honma Sota, Tsutsumi Hayama, Inahashi Yuki, Watanabe Yoshihiro, Nakashima Takuji, Asami Yukihiro, Iwatsuki Masato
O̅mura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
ACS Omega. 2024 Apr 5;9(15):17415-17422. doi: 10.1021/acsomega.4c00145. eCollection 2024 Apr 16.
Utilizing a binding mode-based physicochemical screening method using d-Ala-d-Ala silica gel, two new macrolactams, named banglactams A () and B (), were discovered from the culture broth of K18-0086. In the course of our investigation, we found that d-Ala-d-Ala silica gel precisely differentiated the chemical structures of banglactams and separated them. However, we were not able to obtain enough of to elucidate the structure due to its instability and insolubility. To overcome this challenge, we chemically modified to improve solubility, enabling us to obtain a sufficient material supply for the indirect determination of the structure. Antibacterial activity evaluation of banglactams revealed that binding to d-Ala-d-Ala silica gel exhibited antibacterial activity against ; however, this was not the case with . This research indicates the utility of our original binding mode-based PC screening method, and the combination strategy of PC and chemical modifications led us to discover novel antibacterial compounds.
利用基于结合模式的物理化学筛选方法，使用d-Ala-d-Ala硅胶，从K18-0086的培养液中发现了两种新的大环内酰胺，命名为孟加拉内酰胺A（）和B（）。在我们的研究过程中，我们发现d-Ala-d-Ala硅胶能够精确区分孟加拉内酰胺的化学结构并将它们分离。然而，由于其不稳定性和不溶性，我们无法获得足够的[物质名称未明确]来阐明其结构。为了克服这一挑战，我们对[物质名称未明确]进行了化学修饰以提高其溶解度，从而使我们能够获得足够的材料供应用于间接确定其结构。孟加拉内酰胺的抗菌活性评估表明，与d-Ala-d-Ala硅胶结合的[物质名称未明确]对[细菌名称未明确]具有抗菌活性；然而，[物质名称未明确]并非如此。这项研究表明了我们最初基于结合模式的物理化学筛选方法的实用性，并且物理化学筛选与化学修饰的组合策略使我们发现了新型抗菌化合物。
