A unique transporter of S-adenosylmethionine in African trypanosomes.
African trypanosomes are pathogens of humans and livestock in equatorial Africa. There is a great deal of resistance to present front line drugs for treating African trypanosomiasis such as melarsoprol (Arsobal) and pentamidine. In the search for new and novel drugs against this disease, we have found a unique transporter of S-adenosylmethionine (AdoMet), a metabolite used in transmethylation reactions and polyamine synthesis. This transporter is distinct from those for methionine and adenosine, since AdoMet uptake was not inhibited by trypanocidal drugs, which compete with adenosine for transport. AdoMet analogs competing with [methyl-3H]AdoMet for uptake required a positively charged sulfonium group on the 5' position of the ribose. Since transport of AdoMet does not normally occur to a significant extent in mammalian cells, the parasite transporter provides a selective and novel route to deliver new chemotherapeutic agents against these organisms.
Goldberg
B
B
Haskins Laboratories, Pace University, New York, New York 10038, USA.
Yarlett
N
N
Sufrin
J
J
Lloyd
D
D
Bacchi
C J
CJ
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D009705:Nucleosides / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives / Q000378:metabolism*; D013045:Species Specificity; D014344:Trypanocidal Agents / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D016833:Trypanosoma brucei rhodesiense / Q000378:metabolism*
D002352:Carrier Proteins; D009705:Nucleosides; D014344:Trypanocidal Agents; D012436:S-Adenosylmethionine; D000241:Adenosine