An Enantiodefined Conformationally Constrained Fatty Acid Mimetic and Potent Inhibitor of ToxT.
| Autor: | Markham LE; Department of Chemistry, Dartmouth College, Burke Laboratory, Hanover, New Hampshire 03755, United States., Tolbert JD; Department of Chemistry, Dartmouth College, Burke Laboratory, Hanover, New Hampshire 03755, United States., Kull FJ; Department of Chemistry, Dartmouth College, Burke Laboratory, Hanover, New Hampshire 03755, United States., Midgett CR; Department of Chemistry, Dartmouth College, Burke Laboratory, Hanover, New Hampshire 03755, United States., Micalizio GC; Department of Chemistry, Dartmouth College, Burke Laboratory, Hanover, New Hampshire 03755, United States. |
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| Jazyk: | angličtina |
| Zdroj: | ACS medicinal chemistry letters [ACS Med Chem Lett] 2021 Aug 24; Vol. 12 (9), pp. 1493-1497. Date of Electronic Publication: 2021 Aug 24 (Print Publication: 2021). |
| DOI: | 10.1021/acsmedchemlett.1c00378 |
| Abstrakt: | The chiral conformation that palmitoleic acid takes when it is bound to ToxT, the master regulator of virulence genes in the bacterial pathogen Vibrio cholerae , was used as inspiration to design a novel class of fatty acid mimetics. The best mimetic, based on a chiral hydrindane, was found to be a potent inhibitor of this target. The synthetic chemistry that enabled these studies was based on the sequential use of a stereoselective annulative cross-coupling reaction and dissolving metal reduction to establish the C13 and C9 stereocenters, respectively. Competing Interests: The authors declare no competing financial interest. (© 2021 American Chemical Society.) |
| Databáze: | MEDLINE |
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