917877-27-1Relevant academic research and scientific papers
Delivery of 2-5A cargo into living cells using the Tat cell penetrating peptide: 2-5A-tat
Zhou, Longhu,Thakur, Chandar S.,Molinaro, Ross J.,Paranjape, Jayashree M.,Hoppes, Rieuwert,Jeang, Kuan-Teh,Silverman, Robert H.,Torrence, Paul F.
, p. 7862 - 7874 (2006)
2′,5′-Oligoadenylate tetramer (2-5A) has been chemically conjugated to short HIV-1 Tat peptides to provide 2-5A-tat chimeras. Two different convergent synthetic approaches have been employed to provide such 2-5A-tat bioconjugates. One involved generation
Discovery of novel N -phenylphenoxyacetamide derivatives as EthR inhibitors and ethionamide boosters by combining high-throughput screening and synthesis
Flipo, Marion,Willand, Nicolas,Lecat-Guillet, Nathalie,Hounsou, Candide,Desroses, Matthieu,Leroux, Florence,Lens, Zoé,Villeret, Vincent,Wohlk?nig, Alexandre,Wintjens, René,Christophe, Thierry,Kyoung Jeon, Hee,Locht, Camille,Brodin, Priscille,Baulard, Alain R,Déprez, Benoit
supporting information; experimental part, p. 6391 - 6402 (2012/10/07)
In this paper, we describe the screening of a 14640-compound library using a novel whole mycobacteria phenotypic assay to discover inhibitors of EthR, a transcriptional repressor implicated in the innate resistance of Mycobacterium tuberculosis to the second-line antituberculosis drug ethionamide. From this screening a new chemical family of EthR inhibitors bearing an N-phenylphenoxyacetamide motif was identified. The X-ray structure of the most potent compound crystallized with EthR inspired the synthesis of a 960-member focused library. These compounds were tested in vitro using a rapid thermal shift assay on EthR to accelerate the optimization. The best compounds were synthesized on a larger scale and confirmed as potent ethionamide boosters on M. tuberculosis-infected macrophages. Finally, the cocrystallization of the best optimized analogue with EthR revealed an unexpected reorientation of the ligand in the binding pocket.
