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Binding and Action of Triphenylphosphonium Analog of Chloramphenicol upon the Bacterial Ribosomeстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Chen C-W, Pavlova JA, Lukianov DA, Tereshchenkov AG, Makarov GI, Khairullina ZZ, Tashlitsky VN, Paleskava A., Konevega AL, Bogdanov AA, Osterman IA, Sumbatyan NV, Polikanov YS
- Журнал: Antibiotics
- Том: 10
- Номер: 4
- Год издания: 2021
- Издательство: MDPI Publishing
- Местоположение издательства: Basel, Switzerland, Switzerland
- Номер статьи: 390
- DOI: 10.3390/antibiotics10040390
- Аннотация: Chloramphenicol (CHL) is a ribosome-targeting antibiotic that binds to the peptidyl transferase center (PTC) of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving the properties of this inhibitor, we explored ribosome binding and inhibitory properties of a semi-synthetic triphenylphosphonium analog of CHL—CAM-C4-TPP. Our data demonstrate that this compound exhibits a ~5-fold stronger affinity for the bacterial ribosome and higher potency as an in vitro protein synthesis inhibitor compared to CHL. The X-ray crystal structure of the Thermus thermophilus 70S ribosome in complex with CAM-C4-TPP reveals that, while its amphenicol moiety binds at the PTC in a fashion identical to CHL, the C4-TPP tail adopts an extended propeller-like conformation within the ribosome exit tunnel where it establishes multiple hydrophobic Van der Waals interactions with the rRNA. The synthesized compound represents a promising chemical scaffold for further development by medicinal chemists because it simultaneously targets the two key functional centers of the bacterial ribosome—PTC and peptide exit tunnel.
- Добавил в систему: Сумбатян Наталия Владимировна
Прикрепленные файлы
| № | Имя | Описание | Имя файла | Размер | Добавлен |
|---|---|---|---|---|---|
| 1. | Полный текст | antibiotics-10-00390_LPZaFkM.pdf | 3,7 МБ | 16 сентября 2021 [sumbatyan] | |
| 2. | Полный текст | antibiotics-10-00390.pdf | 3,7 МБ | 16 сентября 2021 [sumbatyan] |