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Issue 38, 2019
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Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis

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Abstract

M. tuberculosis (Mtb) is a pathogenic bacterium that causes tuberculosis, which kills more than 1.5 million people worldwide every year. Strains resistant to available antibiotics pose a significant healthcare problem. The enormous complexity of the ribosome poses a barrier for drug discovery. We have overcome this in a tractable way by using an RNA segment that represents the peptidyl transferase center as a target. By using a novel combination of NMR transverse relaxation times (T2) and computational chemistry approaches, we have obtained improved inhibitors of the Mtb ribosomal PTC. Two phenylthiazole derivatives were predicted by machine learning models as effective inhibitors, and this was confirmed by their IC50 values, which were significantly improved over standard antibiotic drugs.

Graphical abstract: Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis

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Supplementary files

Article information


Submitted
23 May 2019
Accepted
05 Aug 2019
First published
06 Aug 2019

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2019,10, 8764-8767
Article type
Edge Article

Discovery of small-molecule inhibitors targeting the ribosomal peptidyl transferase center (PTC) of M. tuberculosis

B. Tam, D. Sherf, S. Cohen, S. A. Eisdorfer, M. Perez, A. Soffer, D. Vilenchik, S. R. Akabayov, G. Wagner and B. Akabayov, Chem. Sci., 2019, 10, 8764
DOI: 10.1039/C9SC02520K

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