The biochemistry of phosphonate analogues of naturally occurring phosphates.

  • D. J. W. Roach

Student thesis: Doctoral ThesisPhD


6,7 dideoxy-alpha-D-gluco-heptose 7-phosphonic acid, the isosteric phosphonate analogue of naturally-occurring glucose 6-phosphate was synthesised via a novel route, involving the use of an easily-prepared and stable ethyl ester, followed by a facile dealkylation procedure. 6,7 dideoxy alpha-D-gluco-heptose 7-phosphonic acid was shown to behave as a product inhibitor of purified bovine brain hexokinase I, being a competitive inhibitor of MgATP2- and a noncompetitive inhibitor of glucose. 6,7 dideoxy alpha-D-gluco-heptonic 7-phosphonic acid, the isoteric phosphonate analogue of gluconate 6-phosphate was enzymically synthesised from 6,7 dideoxy alpha-D-gluco heptose 7-phosphonic acid and was shown to be a poor substrate for yeast gluconate 6-phosphate dehydrogenase at pH 7.5 and 8.0. 6,7 dideoxy alpha-D-gluco-heptose 7-phosphonic acid had no effect on cell proliferation of mouse lymphoma cells (at mM concentrations) but was found to be more stable then the natural phosphate in their presence. alpha-D-glucose fluorophosphate was tested as an active-site-directed irreversible inhibitor of yeast glucose 6-phosphate dehydrogenase with a view to eventual use of the corresponding phosphonate analogue in similar systems. The fluorophosphate was found to be inactive in this respect.
Date of Award1980
Original languageEnglish
Awarding Institution
  • University of Bath

Cite this