Chemical biology of tetracycline antibiotics.
For more than half a century, tetracycline antibiotics have been used to treat infectious disease. However, what once used to be a commonly prescribed family of antibiotics has now decreased in effectiveness due to wide-spread bacterial resistance. The chemical scaffold of the tetracyclines is a versatile and modifiable structure that is able to interact with many cellular targets. The recent availability of detailed molecular interactions between tetracycline and its cellular targets, along with an understanding of the tetracycline biosynthetic pathway, has provided us with a unique opportunity to usher in a new era of rational drug design. Herein we discuss recent findings that have clarified the mode of action and the biosynthetic pathway of tetracyclines and that have shed light on the chemical biology of tetracycline antibiotics.
Zakeri
Bijan
B
Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, 1200 Main St. W, Hamilton, ON L8N3Z5, Canada.
Wright
Gerard D
GD
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D013754:Tetracyclines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D012335:RNA, Ribosomal; D013754:Tetracyclines