Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets

被引:274
作者
Coombs, GH [1 ]
Goldberg, DE
Klemba, M
Berry, C
Kay, J
Mottram, JC
机构
[1] Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland
[2] Washington Univ, Howard Hughes Med Inst, St Louis, MO 63110 USA
[3] Cardiff Univ, Cardiff CF10 3US, S Glam, Wales
基金
英国惠康基金;
关键词
D O I
10.1016/S1471-4922(01)02037-2
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
All parasitic protozoa contain multiple proteases, some of which are attracting attention as drug targets. Aspartic proteases are already the targets of some clinically useful drugs (e.g. chemotherapy of HIV infection) and a variety of factors make these enzymes appealing to those seeking novel antiparasite therapies. This review provides a critical analysis of the current knowledge on Plasmodium aspartic proteases termed plasmepsins, proposes a definitive nomenclature for this group of enzymes, and compares these enzymes with aspartic proteases of humans and other parasitic protozoa. The present status of attempts to obtain specific inhibitors of the parasite enzymes that will be useful as drugs is outlined and suggestions for future research priorities are proposed.
引用
收藏
页码:532 / 537
页数:6
相关论文
共 42 条
[1]   Expression analysis of BACE2 in brain and peripheral tissues [J].
Bennett, BD ;
Babu-Khan, S ;
Loeloff, R ;
Louis, JC ;
Curran, E ;
Citron, M ;
Vassar, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (27) :20647-20651
[2]   A distinct member of the aspartic proteinase gene family from the human malaria parasite Plasmodium falciparum [J].
Berry, C ;
Humphreys, MJ ;
Matharu, P ;
Granger, R ;
Horrocks, P ;
Moon, RP ;
Certa, U ;
Ridley, RG ;
Bur, D ;
Kay, J .
FEBS LETTERS, 1999, 447 (2-3) :149-154
[3]  
BINGGELI A, 1996, Patent No. 9709311
[4]   Proteolysis of human hemoglobin by schistosome cathepsin D [J].
Brindley, PJ ;
Kalinna, BH ;
Wong, JYM ;
Bogitsh, BJ ;
King, LT ;
Smyth, DJ ;
Verity, CK ;
Abbenante, G ;
Brinkworth, RI ;
Fairlie, DP ;
Smythe, ML ;
Milburn, PJ ;
Bielefeldt-Ohmann, H ;
Zheng, Y ;
McManus, DP .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2001, 112 (01) :103-112
[5]   Parasite proteinases and amino acid metabolism: possibilities for chemotherapeutic exploitation [J].
Coombs, GH ;
Mottram, JC .
PARASITOLOGY, 1997, 114 :S61-S80
[6]   The two sides of enzyme-substrate specificity: lessons from the aspartic proteinases [J].
Dunn, BM ;
Hung, SH .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 2000, 1477 (1-2) :231-240
[7]   Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum [J].
Eggleson, KK ;
Duffin, KL ;
Goldberg, DE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (45) :32411-32417
[8]   MOLECULAR CHARACTERIZATION AND INHIBITION OF A PLASMODIUM-FALCIPARUM ASPARTIC HEMOGLOBINASE [J].
FRANCIS, SE ;
GLUZMAN, IY ;
OKSMAN, A ;
KNICKERBOCKER, A ;
MUELLER, R ;
BRYANT, ML ;
SHERMAN, DR ;
RUSSELL, DG ;
GOLDBERG, DE .
EMBO JOURNAL, 1994, 13 (02) :306-317
[9]   Hemoglobin metabolism in the malaria parasite Plasmodium falciparum [J].
Francis, SE ;
Sullivan, DJ ;
Goldberg, DE .
ANNUAL REVIEW OF MICROBIOLOGY, 1997, 51 :97-123
[10]   Biosynthesis and maturation of the malaria aspartic hemoglobinases plasmepsins I and II [J].
Francis, SE ;
Banerjee, R ;
Goldberg, DE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (23) :14961-14968