PMID: 11310612Apr 20, 2001Paper

Selective inhibition of Trypanosoma brucei GAPDH by 1,3-bisphospho-D-glyceric acid (1,3-diPG) analogues

Bioorganic & Medicinal Chemistry
Sylvain LadameMichèle Willson

Abstract

Various phosphono-phosphates and diphosphonates were synthesized as 1,3-diphosphoglycerate (1,3-diPG) analogues by using a beta-ketophosphonate, an alpha-fluoro,beta-ketophosphonate or a beta-ketophosphoramidate to mimic the unstable carboxyphosphate part of the natural substrate. The inhibitory effect of these analogues on glyceraldehyde-3-phosphate dehydrogenases (GAPDH) from Trypanosoma brucei (Tb) and rabbit muscle were measured with respect to both substrates, glyceraldehyde-3-phosphate (GAP) and 1,3-diPG. Interestingly, all 1,5-diphosphono,2-oxopentanes without substitution at the C-3 position selectively inhibit the Tb GAPDH with respect to 1,3-diPG and are without effect on Rm GAPDH. All 1-phospho,3-oxo,4-phosphonobutanes show themselves to be non-selective inhibitors either with regard to substrates or organisms, but they will be of a great interest as 1,3-diPG stable models for structural studies of co-crystals with GAPDHs.

References

Jan 1, 1987·Annual Review of Microbiology·F R Opperdoes
Sep 1, 1974·The Biochemical Journal·P R Adams, R Harrison
Nov 7, 1998·Journal of Medicinal Chemistry·D L JakemanG M Blackburn
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·A M AronovM H Gelb

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Citations

Nov 26, 2019·Biochemistry. Biokhimii︠a︡·V I MuronetzE V Schmalhausen

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