caa a22 4500 463186850 CHVBK 20180406164856.0 cr unu---uuuuu 170326e20070801xx s 000 0 eng 10.1007/s00726-007-0537-9 doi (NATIONALLICENCE)springer-10.1007/s00726-007-0537-9 Targeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas' disease, and leishmaniasis [Elektronische Daten] [O. Heby, L. Persson, M. Rentala] Summary.: 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 α-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. Springer-Verlag, 2007 Keywords: African sleeping sickness - Chagas' disease - Leishmaniasis - Polyamines nationallicence AbeAdo : 5′-{[(Z)-4-amino-2-butenyl]methylamino}-5′-deoxyadenosine (MDL 73811) nationallicence AdoDATO : S-adenosyl-1,8-diamino-3-thiooctane nationallicence AdoMet : S-adenosylmethionine nationallicence AdoMetDC : S-adenosylmethionine decarboxylase nationallicence APA : 3-aminooxy-1-aminopropane nationallicence CGP 40215A : (bis{[3-(aminoiminomethyl)phenyl]methylene}carbonimidic dihydrazide trihydrochloride) nationallicence CNS : central nervous system nationallicence dcAdoMet : decarboxylated S-adenosylmethionine nationallicence DFMO : DL-α-difluoromethylornithine nationallicence LmPOT1 : Leishmania major polyamine transporter 1 nationallicence MGBG : methylglyoxal-bis(guanylhydrazone) nationallicence MTA : 5′-deoxy-5′-methylthioadenosine nationallicence ODC : ornithine decarboxylase nationallicence SpdS : spermidine synthase nationallicence SpmS : Spermine synthase nationallicence TryR : trypanothione reductase nationallicence TryS : trypanothione synthetase nationallicence Heby O. Department of Molecular Biology, Umeå University, Umeå, Sweden aut Persson L. Department of Experimental Medical Science, BMC, Lund University, Lund, Sweden aut Rentala M. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India aut Amino Acids Springer-Verlag 33/2(2007-08-01), 359-366 0939-4451 33:2<359 2007 33 726 https://doi.org/10.1007/s00726-007-0537-9 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00726-007-0537-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Heby O. Department of Molecular Biology, Umeå University, Umeå, Sweden aut NATIONALLICENCE 700 1- Persson L. Department of Experimental Medical Science, BMC, Lund University, Lund, Sweden aut NATIONALLICENCE 700 1- Rentala M. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India aut NATIONALLICENCE 773 0- Amino Acids Springer-Verlag 33/2(2007-08-01), 359-366 0939-4451 33:2<359 2007 33 726 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer