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Publication Abstract from PubMed

Chloramphenicol (CHL) is an antibiotic targeting the peptidyl transferase center in bacterial ribosomes. We synthesized a new analog, CAM-BER, by substituting the dichloroacetyl moiety of CHL with a positively charged aromatic berberine group. CAM-BER suppresses bacterial cell growth, inhibits protein synthesis in vitro, and binds tightly to the 70S ribosome. Crystal structure analysis reveals that the bulky berberine group folds into the P site of the peptidyl transferase center (PTC), where it competes with the formyl-methionine residue of the initiator tRNA. Our toe-printing data confirm that CAM-BER acts as a translation initiation inhibitor in stark contrast to CHL, a translation elongation inhibitor. Moreover, CAM-BER induces a distinct rearrangement of conformationally restrained nucleotide A2059, suggesting that the 23S rRNA plasticity is significantly higher than previously thought. CAM-BER shows potential in avoiding CHL resistance and presents opportunities for developing novel berberine derivatives of CHL through medicinal chemistry exploration.

Berberine analog of chloramphenicol exhibits a distinct mode of action and unveils ribosome plasticity.,Batool Z, Pavlova JA, Paranjpe MN, Tereshchenkov AG, Lukianov DA, Osterman IA, Bogdanov AA, Sumbatyan NV, Polikanov YS Structure. 2024 Jul 6:S0969-2126(24)00231-4. doi: 10.1016/j.str.2024.06.013. PMID:39019034^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.