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Lipid II as a Target for Novel Antibiotics:Structural and Molecular Dynamics Studies.
The growing problem of antibiotic resistance in medicine raises the attention to antimicrobial substances that act on non-protein molecules, which have more conservative structure comparing to proteins or peptides. One of the most promising and studied targets is lipid II — the participant of the bacterial cell wall biosynthetic pathway. Lipid II is present in the bacterial membrane only and has a conservative chemical structure. There are several classes of natural antibiotics acting on lipid II, some of which block the peptidoglycan synthesis by formation of a strong complex with lipid II, and others have an additional bactericidal mechanism involved a violation of the membrane integrity. This review examines the prospects for using such antibacterial substances as new drugs to combat antibiotic-resistant pathogens. The main emphasis is made on the studies of membrane-embedded lipid II structure and molecular mechanisms of its recognition by water-soluble antibiotics, and also on computer modelling of their interaction.