Drug discovery strategies to outer membrane targets in Gram-negative pathogens

• Published in: Bioorganic & medicinal chemistry Vol. 24; no. 24; pp. 6320 - 6331
• Main Author: Brown, Dean G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-12-2016
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial; Bacterial Outer Membrane Proteins - antagonists & inhibitors; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - metabolism; Drug Discovery; Gram-negative; Gram-Negative Bacteria - drug effects; Gram-Negative Bacteria - metabolism; Lipid A; Lipopolysaccharide; Microbial Sensitivity Tests; Outer membrane; Lipopolysaccharide; Antibacterial; Gram-negative; Outer membrane; Lipid A
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2016.05.004

This review article summarizes important chemical and structural advances in Gram-negative outer membrane targets within the key pathways of lipopolysaccharide, outer membrane proteins and lipoproteins. [Display omitted]
This review will cover selected recent examples of drug discovery strategies which target the outer membrane (OM) of Gram-negative bacteria either by disruption of outer membrane function or by inhibition of essential gene products necessary for outer membrane assembly. Significant advances in pathway elucidation, structural biology and molecular inhibitor designs have created new opportunities for drug discovery within this target-class space.