SF2312 is a natural phosphonate inhibitor of Enolase

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SF2312 is a natural phosphonate inhibitor of Enolase

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Title: SF2312 is a natural phosphonate inhibitor of Enolase
Author: Leonard, Paul G.; Satani, Nikunj; Maxwell, David; Lin, Yu-Hsi; Hammoudi, Naima; Peng, Zhenghong; Pisaneschi, Federica; Link, Todd M.; Lee, Gilbert R.; Sun, Duoli; Prasad, Basvoju A. Bhanu; Di Francesco, Maria Emilia; Czako, Barbara; Asara, John M.; Wang, Y. Alan; Bornmann, William; DePinho, Ronald A.; Muller, Florian L.

Note: Order does not necessarily reflect citation order of authors.

Citation: Leonard, P. G., N. Satani, D. Maxwell, Y. Lin, N. Hammoudi, Z. Peng, F. Pisaneschi, et al. 2016. “SF2312 is a natural phosphonate inhibitor of Enolase.” Nature chemical biology 12 (12): 1053-1058. doi:10.1038/nchembio.2195. http://dx.doi.org/10.1038/nchembio.2195.
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Abstract: Despite being critical for energy generation in most forms of life, few if any microbial antibiotics specifically inhibit glycolysis. To develop a specific inhibitor of the glycolytic enzyme Enolase 2 for the treatment of cancers with deletion of Enolase 1, we modeled the synthetic tool compound inhibitor, Phosphonoacetohydroxamate (PhAH) into the active site of human ENO2. A ring-stabilized analogue of PhAH, with the hydroxamic nitrogen linked to the alpha-carbon by an ethylene bridge, was predicted to increase binding affinity by stabilizing the inhibitor in a bound conformation. Unexpectedly, a structure based search revealed that our hypothesized back-bone-stabilized PhAH bears strong similarity to SF2312, a phosphonate antibiotic of unknown mode of action produced by the actinomycete Micromonospora, which is active under anaerobic conditions. Here, we present multiple lines of evidence, including a novel X-ray structure, that SF2312 is a highly potent, low nM inhibitor of Enolase.
Published Version: doi:10.1038/nchembio.2195
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110371/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630605
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