Bacterial type I signal peptidase inhibitors - Optimized hits from nature

Eur J Med Chem. 2022 May 26;238:114490. doi: 10.1016/j.ejmech.2022.114490. Online ahead of print.ABSTRACTThe ever-increasing number of bacteria resistant to the currently available antibacterial agents is a great medical problem today, and new antibiotics with novel mechanisms of action are urgently needed. Among the validated antibacterial drug targets against which new classes of antibiotics might be directed is bacterial type I signal peptidase (SPase I), an essential part of the Tat and Sec secretory systems. SPase I is responsible for the hydrolysis of the N-terminal signal peptides from proteins secreted across the cytoplasmic membrane and plays a key role in bacterial viability and virulence. This review focuses on the antibacterial activity of natural and synthetic SPase I inhibitors reported to date, namely β-lactams, lipopeptides, and arylomycins, but also an example of SPase I activator was presented.PMID:35660251 | DOI:10.1016/j.ejmech.2022.114490

Source: European Journal of Medicinal Chemistry - June 6, 2022 Category: Chemistry Authors: Natalia Sza łaj Andrea Benediktsdottir Dominika Rusin Anders Karl én Sherry L Mowbray Anna Wi ęckowska Source Type: research