Selection and properties of Leishmania tropica resistant to 10-propargyl-5,8-dideazafolate, an inhibitor of thymidylate synthetase

摘要: Leishmania tropica promastigotes have been selected which are highly resistant to the thymidylate synthetase (TS) inhibitor, 10-propargyl-5,8-dideazafolate (CB3717). As reported for L. methotrexate (MTX), an inhibitor of dihydrofolate reductase (DHFR), CB3717-resistant organisms high levels bifunctional TS-DHFR and amplified DNA sequences. represents up 2% protein in cell extracts does not appear a structural alteration that contributes drug resistance. The unit has uniform restriction-site map throughout selection is nearly identical 30 kb R-region found MTX-resistant cells, except small increase size fragment contains junction believed be site rearrangements generated during amplification. cells do possess H-region cells. low CB3717 appears as 30-kb extrachromosomal circle, similar organisms. In higher drug, appeared molecular weight forms. When were grown absence gradually fell approximately 10% levels. These findings support proposal possesses sequences encode protein.