AdoHcy hydrolase of Trichomonas vaginalis: studies of the effects of 5'-modified adenosine analogues and related 6-N-cyclopropyl derivatives.
Trypanosoma brucei and Trichomonas vaginalis are both parasitic protozoans that are known to share many similar biochemical pathways. Aristeromycin, as well as 5'-iodovinyl and 5'-oxime analogues of adenosine, are potent inhibitors of AdoHcy hydrolase in T. brucei, an enzyme that catalyses the hydrolysis of AdoHcy to adenosine and L-homocysteine. To help determine the role of this enzyme in T. vaginalis, we have tested a library of 5'-modified adenosine derivatives, including 5'-deoxy-5'-(iodomethylene)-adenosine and related 6-N-cyclopropyl analogues. Our results indicate that these inhibitors are effective at inhibiting the growth of T. vaginalis, by as much as 95%.
Department of Biological Sciences, University of the Pacific, Stockton, CA 95211, USA.
Padraick J
PJ
Dornbush
Guillermo
G
Vazquez-Anaya
Ajit
A
Shokar
Saoly
S
Benson
Magdalena
M
Rapp
Stanislaw F
SF
Wnuk
Lisa A
LA
Wrischnik
Kirkwood M
KM
Land
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000595:Amino Acid Sequence; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003521:Cyclopropanes / Q000737:chemistry*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014246:Trichomonas vaginalis / Q000201:enzymology*
D000981:Antiprotozoal Agents; D003521:Cyclopropanes; C030034:aristeromycin; C021985:cyclopropene; D043383:Adenosylhomocysteinase; D000241:Adenosine