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Targeting the polya...
Targeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas' disease, and leishmaniasis
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- Heby, Olle (författare)
- Umeå universitet,Umeå University,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Heby
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- Persson, Lo (författare)
- Lund University,Lunds universitet,Biogena aminer,Forskargrupper vid Lunds universitet,Biogenic Amines,Lund University Research Groups
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- Rentala, M. (författare)
- Jawaharlal Nehru University
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(creator_code:org_t)
- 2007-07-04
- 2007
- Engelska.
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Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 33:2, s. 359-366
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Trypanosomatids depend on spermidine for growth and survival. Consequently, enzymes involved in spermidine synthesis and utilization, i.e. arginase, ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (AdoMetDC), spermidine synthase, trypanothione synthetase (TryS), and trypanothione reductase (TryR), are promising targets for drug development. The ODC inhibitor alpha-difluoromethylornithine (DFMO) is about to become a first-line drug against human late-stage gambiense sleeping sickness. Another ODC inhibitor, 3-aminooxy-1-aminopropane (APA), is considerably more effective than DFMO against Leishmania promastigotes and amastigotes multiplying in macrophages. AdoMetDC inhibitors can cure animals infected with isolates from patients with rhodesiense sleeping sickness and leishmaniasis, but have not been tested on humans. The antiparasitic effects of inhibitors of polyamine and trypanothione formation, reviewed here, emphasize the relevance of these enzymes as drug targets. By taking advantage of the differences in enzyme structure between parasite and host, it should be possible to design new drugs that can selectively kill the parasites.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- African sleeping sickness
- Chagas' disease
- leishmaniasis
- polyamines
- African sleeping sickness
Publikations- och innehållstyp
- for (ämneskategori)
- ref (ämneskategori)
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