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Competitive inhibit...
Competitive inhibitors of type B ribose 5-phosphate isomerases : design, synthesis and kinetic evaluation of new D-allose and D-allulose 6-phosphate derivatives
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Mariano, Sandrine (author)
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- Roos, Annette K. (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Mowbray, Sherry L. (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylärbiologi,Department of Molecular Biology
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Salmon, Laurent (author)
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(creator_code:org_t)
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- Elsevier BV, 2009
- 2009
- English.
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In: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 344:7, s. 869-880
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://res.slu.se/i...
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Abstract
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- This study reports syntheses Of D-allose 6-phosphate (All6P), D-allulose (or D-psicose) 6-phosphate (Allu6P), and seven D-ribose 5-phosphate isomerase (Rpi) inhibitors. The inhibitors were designed as analogues of the 6-carbon high-energy intermediate postulated for the All6P to Allu6P isomerization reaction (Allpi activity) catalyzed by type B Rpi from Escherichia coli (EcRpiB). 5-PhosphO-D-ribonate, easily obtained through oxidative cleavage of either All6P or Allu6P, led to the original synthon 5-dihydrogenopliospho-D-ribono-1,4-lactone from which the other inhibitors could be synthesized through nucleophilic addition in one step. Kinetic evaluation on Allpi activity of EcRpiB shows that two of these compounds. 5phospho-D-ribonohydroxamic acid and N-(5-phospho-D-ribonoyl)-methylamine, indeed behave as new efficient inhibitors of EcRpiB; further, 5-phospho-D-ribonohydroxamic acid was demonstrated to have competitive inhibition. Kinetic evaluation on Rpi activity of both EcRpiB and RpiB from Mycobacterium tuberculosis (MtRpiB) shows that several of the designed 6-carbon high-energy intermediate analogues are new competitive inhibitors of both RpiBs. One of them, 5-phospho-D-ribonate, not only appears as the strongest competitive inhibitor of a Rpi ever reported in the literature, with a K-i value of 9 mu M for MtRpiB, but also displays specific inhibition of MtRpiB versus EcRpiB.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Keyword
- Sugar phosphates
- Enzyme inhibitor
- Hydroxamic acids
- Ribose 5-phosphate isomerase
- Allose 6-phosphate isomerase
- Mycobacterium tuberculosis
- Biology
- Biologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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