A unique transporter of S-adenosylmethionine in African trypanosomes

被引:30
作者
Goldberg, B
Yarlett, N
Sufrin, J
Lloyd, D
Bacchi, CJ
机构
[1] PACE UNIV,HASKINS LABS,NEW YORK,NY 10038
[2] PACE UNIV,DEPT CHEM & PHYS SCI,NEW YORK,NY 10038
[3] PACE UNIV,DEPT BIOL,NEW YORK,NY 10038
[4] UNIV WALES COLL CARDIFF,CARDIFF CF1 3TL,S GLAM,WALES
[5] ROSWELL PK CANC INST,GRACE CANC DRUG CTR,BUFFALO,NY 14263
关键词
purine uptake; S-adenosylmethionine metabolism; trypanocidal agents;
D O I
10.1096/fasebj.11.4.9068614
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
African trypanosomes are pathogens of humans and livestock in equatorial Africa, There is a great deal of resistance tea 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-H-3]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., Yarlett N., Sufrin, J., Lloyd, D., Baechi, C. J. A unique transporter of S-adenosyhmethionine in African trypanosomes.
引用
收藏
页码:256 / 260
页数:5
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