{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T05:40:10Z","timestamp":1791610810311,"version":"4.3.4"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,5,22]]},"abstract":"<jats:p>\n                    The drugs in clinical use against African sleeping sickness are\n toxic, costly, or inefficient. We show that\n                    <jats:italic>Trypanosoma\n brucei<\/jats:italic>\n                    , which causes this disease, has very low levels of CTP,\n which are due to a limited capacity for\n                    <jats:italic>de novo<\/jats:italic>\n                    synthesis and the lack of salvage pathways. The CTP synthetase\n inhibitors 6-diazo-5-oxo-\n                    <jats:sc>l<\/jats:sc>\n                    -norleucine (DON) and\n \u03b1-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin)\n reduced the parasite CTP levels even further and inhibited trypanosome\n proliferation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in\n                    <jats:italic>T.\n brucei-<\/jats:italic>\n                    infected mice. In mammalian cells, DON mainly inhibits\n                    <jats:italic>de novo<\/jats:italic>\n                    purine biosynthesis, a pathway lacking in\n trypanosomes. We could rescue DON-treated human and mouse fibroblasts\n by the addition of the purine base hypoxanthine to the growth medium.\n For treatment of sleeping sickness, we propose the use of CTP\n synthetase inhibitors alone or in combination with appropriate\n nucleosides or bases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.111139498","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"6412-6416","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":107,"title":["<i>Trypanosoma brucei<\/i>\n                    CTP synthetase: A target for the treatment of African sleeping sickness"],"prefix":"10.1073","volume":"98","author":[{"given":"Anders","family":"Hofer","sequence":"first","affiliation":[{"name":"Medical Biochemistry, Department of Medical Biosciences, Ume\u00e5\r University, SE-901 87 Ume\u00e5, Sweden; Department of\r Parasitology, University 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