Glycolysis as a target for the design of new anti-trypanosome drugs.
Glycolysis is perceived as a promising target for new drugs against parasitic trypanosomatid protozoa because this pathway plays an essential role in their ATP supply. Trypanosomatid glycolysis is unique in that it is compartmentalized, and many of its enzymes display unique structural and kinetic features. Structure- and catalytic mechanism-based approaches are applied to design compounds that inhibit the glycolytic enzymes of the parasites without affecting the corresponding proteins of the human host. For some trypanosomatid enzymes, potent and selective inhibitors have already been developed that affect only the growth of cultured trypanosomatids, and not mammalian cells.
Verlinde
C L
CL
Department of Biological Structure, Biomolecular Structure Center, University of Washington, Seattle, USA.
Hannaert
V
V
Blonski
C
C
Willson
M
M
Périé
J J
JJ
Fothergill-Gilmore
L A
LA
Opperdoes
F R
FR
Gelb
M H
MH
Hol
W G
WG
Michels
P A
PA
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007535:Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007891:Leishmania / Q000187:drug effects / Q000201:enzymology; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000201:enzymology
D004791:Enzyme Inhibitors; D014344:Trypanocidal Agents; D010770:Phosphotransferases; D007535:Isomerases