Abstract |
The separation by chromatofocusing of two distinct purine nucleoside cleaving activities from crude extracts of Trypanosoma brucei brucei is described. One catalyzes the reversible phosphorolysis of 5'-deoxy-5'-methylthioadenosine (MeSAdo) and adenosine ( Ado) and was designated an MeSAdo/ Ado phosphorylase, while the other catalyzes the hydrolysis of adenosine, inosine, and guanosine but not MeSAdo. The substrate specificity of trypanosomal MeSAdo/ Ado phosphorylase differed from that of a mammalian MeSAdo phosphorylase (derived from murine Sarcoma 180 cells) in that it was able to phosphorolyze 2'-deoxyadenosine, 3'-deoxyadenosine and 2',3'-dideoxyadenosine. In addition, the trypanosomal phosphorylase was able to utilize the nucleoside analog, 6-methylpurine 2'-deoxyribonucleoside, as an alternative substrate, whereas the mammalian enzyme could not. Because of these differences, cytotoxic analogs of MeSAdo may be designed that are selectively activated by the trypanosomal MeSAdo/ Ado phosphorylase.
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Authors | L Y Ghoda, T M Savarese, C H Northup, R E Parks Jr, J Garofalo, L Katz, B B Ellenbogen, C J Bacchi |
Journal | Molecular and biochemical parasitology
(Mol Biochem Parasitol)
Vol. 27
Issue 2-3
Pg. 109-18
(Jan 15 1988)
ISSN: 0166-6851 [Print] Netherlands |
PMID | 3125430
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Deoxyadenosines
- Neoplasm Proteins
- Purines
- Thionucleosides
- 5'-methylthioadenosine
- Pentosyltransferases
- Purine-Nucleoside Phosphorylase
- 5'-methylthioadenosine phosphorylase
- N-Glycosyl Hydrolases
- purine nucleosidase
- Adenosine
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Topics |
- Adenosine
(analogs & derivatives, metabolism)
- Animals
- Deoxyadenosines
- Mice
(metabolism)
- N-Glycosyl Hydrolases
(metabolism)
- Neoplasm Proteins
(metabolism)
- Pentosyltransferases
(metabolism)
- Purine-Nucleoside Phosphorylase
(metabolism)
- Purines
(metabolism)
- Sarcoma 180
(enzymology)
- Species Specificity
- Substrate Specificity
- Thionucleosides
(metabolism)
- Trypanosoma brucei brucei
(enzymology)
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