Competitive inhibitors of type B ribose 5-phosphate isomerases: design, synthesis and kinetic evaluation of new D-allose and D-allulose 6-phosphate derivatives

Competitive inhibitors of type B ribose 5-phosphate isomerases : design, synthesis and kinetic evaluation of new D-allose and D-allulose 6-phosphate derivatives

Mariano, Sandrine (författare)

Roos, Annette K. (författare): Uppsala universitet,Institutionen för cell- och molekylärbiologi

Mowbray, Sherry L. (författare): Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylärbiologi,Department of Molecular Biology

Salmon, Laurent (författare)

(creator_code:org_t)

Elsevier BV, 2009
2009
Engelska.
Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 344:7, s. 869-880

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Abstract Ämnesord

Stäng

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.

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)

Av författaren/redakt...: Mariano, Sandrin ...; Roos, Annette K.; Mowbray, Sherry ...; Salmon, Laurent

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