Tetrahydrobenzothiophene derivatives: conformationally restricted inhibitors of type II dehydroquinase

Paz, S. et al. (2011) Tetrahydrobenzothiophene derivatives: conformationally restricted inhibitors of type II dehydroquinase. ChemMedChem, 6(2), pp. 266-272. (doi: 10.1002/cmdc.201000343)

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Publisher's URL: http://dx.doi.org/10.1002/cmdc.201000343


Restriction is good for inhibition! Tetrahydrobenzothiophene-derived rigid mimics of the type II dehydroquinase (DHQ2)-catalyzed reaction intermediate are reported. These derivatives fix the interaction with the tyrosine, the base that initiates the enzymatic reaction, in an inappropriate orientation for catalysis. Two competitive inhibitors in the series, 2-propenyl derivative 5 e and 2-cyclopropylethyl compound 5 i (shown), were crystallized in complex with DHQ2 from <i>Helicobacter pylori</i>, and the X-ray structures were determined at 1.95Å and 1.85Å, respectively.

Item Type:Articles
Keywords:Competitive inhibitors, Helicobacter pylori, Mycobacterium tuberculosis, restricted conformation, stable ozonides
Glasgow Author(s) Enlighten ID:Lapthorn, Dr Adrian
Authors: Paz, S., Tizón, L., Otero, J.M., Llamas-Saiz, A.L., Fox, G.C., van Raaij, M.J., Lamb, H., Hawkins, A.R., Lapthorn, A.J., Castedo, L., and González-Bello, C.
Subjects:Q Science > QD Chemistry
College/School:College of Science and Engineering > School of Chemistry
Journal Name:ChemMedChem
ISSN (Online):1860-7187
Published Online:10 November 2010
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