Polyamine biosynthetic enzymes as drug targets in parasitic protozoa

被引:73
作者
Heby, O [1 ]
Roberts, SC
Ullman, B
机构
[1] Umea Univ, Dept Mol Biol, SE-90187 Umea, Sweden
[2] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA
关键词
African sleeping sickness; Chagas' disease; leishmaniasis; malaria; polyamine;
D O I
10.1042/BST0310415
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Molecular, biochemical and genetic characterization of ornithine decarboxylase, S-adenosylmethionine decarboxylase and spermidine synthase establishes that these polyamine-biosynthetic enzymes are essential for growth and survival of the agents that cause African sleeping sickness, Chagas' disease, leishmaniasis and malaria. These enzymes exhibit features that differ significantly between the parasites and the human host. Therefore it is conceivable that exploitation of such differences can lead to the design of new inhibitors that will selectively kill the parasites while exerting minimal, or at least tolerable, effects on the parasite-infected patient.
引用
收藏
页码:415 / 419
页数:5
相关论文
共 32 条
[1]   POLYAMINE METABOLISM - A POTENTIAL THERAPEUTIC TARGET IN TRYPANOSOMES [J].
BACCHI, CJ ;
NATHAN, HC ;
HUTNER, SH .
SCIENCE, 1980, 210 (4467) :332-334
[2]   CURE OF MURINE TRYPANOSOMA-BRUCEI-RHODESIENSE INFECTIONS WITH AN S-ADENOSYLMETHIONINE DECARBOXYLASE INHIBITOR [J].
BACCHI, CJ ;
NATHAN, HC ;
YARLETT, N ;
GOLDBERG, B ;
MCCANN, PP ;
BITONTI, AJ ;
SJOERDSMA, A .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1992, 36 (12) :2736-2740
[3]   PLASMODIUM-FALCIPARUM AND PLASMODIUM-BERGHEI - EFFECTS OF ORNITHINE DECARBOXYLASE INHIBITORS ON ERYTHROCYTIC SCHIZOGONY [J].
BITONTI, AJ ;
MCCANN, PP ;
SJOERDSMA, A .
EXPERIMENTAL PARASITOLOGY, 1987, 64 (02) :237-243
[4]   In vitro trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors [J].
Brun, R ;
Buhler, Y ;
Sandmeier, U ;
Kaminsky, R ;
Bacchi, CJ ;
Rattendi, D ;
Lane, S ;
Croft, SL ;
Snowdon, D ;
Yardley, V ;
Caravatti, G ;
Frei, J ;
Stanek, J ;
Mett, H .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1996, 40 (06) :1442-1447
[5]   ANTITRYPANOSOMAL EFFECTS OF POLYAMINE BIOSYNTHESIS INHIBITORS CORRELATE WITH INCREASES IN TRYPANOSOMA-BRUCEI-BRUCEI S-ADENOSYL-L-METHIONINE [J].
BYERS, TL ;
BUSH, TL ;
MCCANN, PP ;
BITONTI, AJ .
BIOCHEMICAL JOURNAL, 1991, 274 :527-533
[6]   Trypanosoma cruzi epimastigotes lack ornithine decarboxylase but can express a foreign gene encoding this enzyme [J].
Carrillo, C ;
Cejas, S ;
Gonzalez, NS ;
Algranati, ID .
FEBS LETTERS, 1999, 454 (03) :192-196
[7]   Sensitivity of trypanosomatid protozoa to DFMO and metabolic turnover of ornithine decarboxylase [J].
Carrillo, C ;
Cejas, S ;
Cortés, M ;
Ceriani, C ;
Huber, A ;
González, NS ;
Algranati, ID .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 279 (02) :663-668
[8]  
Cohen S.S., 1998, GUIDE POLYAMINES
[9]   The crystal structure of human S-adenosylmethionine decarboxylase at 2.25 Å resolution reveals a novel fold [J].
Ekstrom, JL ;
Mathews, II ;
Stanley, BA ;
Pegg, AE ;
Ealick, SE .
STRUCTURE, 1999, 7 (05) :583-595
[10]  
Fairlamb Alan H., 1997, P149