Abstract
5-Deoxy-5-phospho-d-ribonohydroxamic acid, a mimic of the 1,2-cis-enediolate high-energy intermediate species of the allose-6-phosphate isomerase reaction, was obtained by a six-step synthesis from d-erythronolactone. In contrast to the known competitive ribose-5-phosphate isomerase (Rpi) inhibitors 4-deoxy-4-phospho-d-erythronohydroxamic acid, 4-deoxy-4-phospho-d-erythronate, and 4-deoxy-4-phosphonomethyl-d-erythronate, the new hydroxamic acid selectively inhibits Mycobacterium tuberculosis RpiB (Ki = 0.40 mM, Km/Ki = 4.5) versus Spinacia oleracea RpiA, and hence appears as a promising lead for the design of potent species-specific inhibitors of the bacterial enzyme.
Original language | English (US) |
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Pages (from-to) | 3691-3694 |
Number of pages | 4 |
Journal | Tetrahedron Letters |
Volume | 46 |
Issue number | 21 |
DOIs | |
State | Published - May 23 2005 |
Externally published | Yes |
Keywords
- 5-Phosphate D-ribose isomerase
- 6-Phosphate D-allose isomerase
- Competitive inhibitor
- Phosphate sugar
- RpiB
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry