TY - JOUR
T1 - Two novel nucleobase/pentamidine transporters from Trypanosoma brucei
AU - Ortiz, Diana
AU - Sanchez, Marco
AU - Quecke, Paula
AU - Landfear, Scott M.
N1 - Funding Information:
This work was supported by NIH grant AI44138 to SML. We thank Dr. Robert Perkins of Portland State University for performing inductively coupled mass spectrometry experiments, and Dr. Najib El-Sayed for discussions concerning ENT family members in GeneDB. We thank the Research Triangle Institute International (Research Triangle Park, NC) for a gift of [ 14 C]pentamidine obtained under the support of the Drug Synthesis and Chemistry Branch, National Cancer Institute. We thank Cosmo Buffalo for studies on functional expression of TbNT3 and TbNT4 in Leishmania null mutants.
PY - 2009/2
Y1 - 2009/2
N2 - African trypanosomes are unable to synthesize purines de novo and must salvage preformed purine nucleosides and nucleobases from their hosts. The Trypanosoma brucei genome project has identified 12 members of the equilibrative nucleoside transporter family, most of which have been characterized previously as nucleoside and/or nucleobase transporters. Here the 11th member of this family, TbNT11.1, has been functionally expressed in null mutants of Leishmania that are deficient in purine nucleoside or nucleobase uptake and identified as a high-affinity purine nucleobase transporter. Expression of TbNT11.1 in Xenopus oocytes revealed that it is also a transporter for the diamidine drug pentamidine that is the principal drug employed to treat early stage human African trypanosomiasis and may thus contribute to the uptake of this therapeutically important compound. In addition, characterization of the 12th member of the family, TbNT12.1, reveals that it is an adenine/pentamidine transporter.
AB - African trypanosomes are unable to synthesize purines de novo and must salvage preformed purine nucleosides and nucleobases from their hosts. The Trypanosoma brucei genome project has identified 12 members of the equilibrative nucleoside transporter family, most of which have been characterized previously as nucleoside and/or nucleobase transporters. Here the 11th member of this family, TbNT11.1, has been functionally expressed in null mutants of Leishmania that are deficient in purine nucleoside or nucleobase uptake and identified as a high-affinity purine nucleobase transporter. Expression of TbNT11.1 in Xenopus oocytes revealed that it is also a transporter for the diamidine drug pentamidine that is the principal drug employed to treat early stage human African trypanosomiasis and may thus contribute to the uptake of this therapeutically important compound. In addition, characterization of the 12th member of the family, TbNT12.1, reveals that it is an adenine/pentamidine transporter.
KW - African trypanosomes
KW - Nucleobase transporters
KW - Pentamidine
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U2 - 10.1016/j.molbiopara.2008.09.011
DO - 10.1016/j.molbiopara.2008.09.011
M3 - Article
C2 - 18992774
AN - SCOPUS:57849141140
SN - 0166-6851
VL - 163
SP - 67
EP - 76
JO - Molecular and Biochemical Parasitology
JF - Molecular and Biochemical Parasitology
IS - 2
ER -