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Review
. 2020 Jun:220:114-121.
doi: 10.1016/j.trsl.2020.02.001. Epub 2020 Feb 6.

Structural approaches to pathway-specific antimicrobial agents

Michael E Johnson  1 , Leslie W-M Fung  2
Affiliations
Review

Structural approaches to pathway-specific antimicrobial agents

Michael E Johnson et al. Transl Res. 2020 Jun.

Abstract

This perspective provides an overview of the evolution of antibiotic discovery from a largely phenotypic-based effort, through an intensive structure-based design focus, to a more holistic approach today. The current focus on antibiotic development incorporates assay and discovery conditions that replicate the host environment as much as feasible. They also incorporate several strategies, including target identification and validation within the whole cell environment, a variety of target deconvolution methods, and continued refinement of structure-based design approaches.

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Figures

Scheme 1.
Scheme 1.
Examples of Golden Age antibiotic discovery.
Scheme 2.
Scheme 2.
Essential genes of B. subtilis and examples of inhibitors from structure-based design against specific enzymatic targets.
Scheme 3.
Scheme 3.
Examples of antibiotic potentiation against resistant strains.
Scheme 4.
Scheme 4.
New directions for improvement in target identification and validation.
See this image and copyright information in PMC

References

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