Inhibition of protein synthesis occurring on tetracycline-resistant, TetM-protected ribosomes by a novel class of tetracyclines, the glycylcyclines.
One of the two major mechanisms of tetracycline resistance is ribosomal protection. Of this resistance type, tet(M) is the best characterized. Although the mechanism of tet(M) resistance has not yet been fully elucidated, it has been demonstrated that ribosomes isolated from a tet(M) strain are resistant to inhibition of protein synthesis by tetracycline. A new generation of tetracycline compounds, the glycylcyclines, that are able to inhibit protein synthesis occurring on tetracycline-resistant, TetM-protected ribosomes, as well as wild-type, tetracycline-sensitive ribosomes, have been identified.
Rasmussen
B A
BA
Department of Molecular Biology, American Cyanamid Company, Pearl River, New York 10965.
Gluzman
Y
Y
Tally
F P
FP
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D004269:DNA, Bacterial / Q000096:biosynthesis; D004926:Escherichia coli / Q000378:metabolism; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012329:RNA, Bacterial / Q000096:biosynthesis; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D013753:Tetracycline Resistance / Q000235:genetics*; D013754:Tetracyclines / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D013462:Sulfur Radioisotopes; D013754:Tetracyclines; C085305:9-(N,N-dimethylglycylamido)minocycline; C085306:6-demethyl-9-(N,N-dimethylglycylamido)-6-deoxytetracycline; D008911:Minocycline