{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:12:05Z","timestamp":1768911125417,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,2,19]],"date-time":"2004-02-19T00:00:00Z","timestamp":1077148800000},"content-version":"vor","delay-in-days":4797,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[1991,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:sc>DL<\/jats:sc>\u2010\u03b1\u2010Difluoromethylornithine (DFMO), a suicide inhibitor of eukaryotic ornithine decarboxylase (ODC), has therapeutic activities against African trypanosomiasis. The K<jats:sub>i<\/jats:sub>, value of DFMO for ODC of <jats:italic>Trypanosoma brucei<\/jats:italic> is somewhat higher than that for mouse ODC. The therapeutic efficacy of DFMO cannot therefore be attributed to a preferential inhibition of the parasite enzyme. The <jats:italic>T. brucei<\/jats:italic> gene encoding ODC was cloned and sequenced, and the derived amino acid sequence has 61.5% homology with that of mouse ODC, except that the C\u2010terminal 36 amino acids of the mouse enzyme are missing from the parasite enzyme. The cloned <jats:italic>T. brucei<\/jats:italic> and mouse ODC genes were expressed in ODC\u2010deficient Chinese hamster ovary cells (CHO) where the <jats:italic>T. brucei<\/jats:italic> enzyme was stable, but mouse ODC was unstable. Thus, the observed difference in intracellular stability is a property of the ODC protein itself, rather than of the cellular environment in which it is expressed. A chimeric ODC composed of the amino terminus of trypanosome ODC and the C\u2010terminus of mouse ODC also was rapidly degraded in CHO cells, suggesting that peptide sequences in the mouse ODC carboxy\u2010terminus determine its stability.<\/jats:p><jats:p>The relatively slow turnover of the parasite enzyme constitutes the basis of selective antitrypanosomal action of DFMO. By this same token, many other proteins known to perform crucial functions in bacteria, fungi, protozoa, helminths, etc., also may have shorter half\u2010lives in the mammalian hosts than in parasites. Suicide inhibitors of these proteins may have desirable characteristics as good chemotherapeutic agents. This new approach could provide an additional strategy for controlling infectious diseases.<\/jats:p>","DOI":"10.1002\/jcb.240450111","type":"journal-article","created":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T00:51:29Z","timestamp":1117241489000},"page":"49-53","source":"Crossref","is-referenced-by-count":15,"title":["A novel suicide inhibitor strategy for antiparasitic drug development"],"prefix":"10.1002","volume":"45","author":[{"given":"C. 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