THE DIHYDROFOLATE-REDUCTASE THYMIDYLATE SYNTHETASE GENE IN THE DRUG-RESISTANCE OF MALARIA PARASITES

被引：133

作者：

HYDE, JE

机构：

[1] Department of Biochemistry and Applied Molecular Biology, University of Manchester Institute of Sciences and Technology (UMIST), Manchester, M60 1QD

来源：

PHARMACOLOGY & THERAPEUTICS | 1990年 / 48卷 / 01期

关键词：

D O I：

10.1016/0163-7258(90)90017-V

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Resistance to antifolate drugs such as pyrimethamine is widespread among malaria parasites of the most pathogenic species Plasmodium falciparum. These drugs inhibit the dihydrofolate reductase activity of the dihydrofolate reductase-thymidylate synthetase (DHFR-TS) bifunctional enzyme. This review examines work done to characterize the enzyme, the cloning of plasmodial DHFR-TS genes, chromosomal mapping studies of these genes by pulsed-field gel electrophoresis, and the structural insights into the mechanism of drug resistance that have been gained by comparing genes from drug-sensitive parasites with those from drug-resistant strains that have arisen in the field or after the experimental induction. © 1990.

引用

页码：45 / 59

页数：15

共 77 条

[1]

ALT FW, 1978, J BIOL CHEM, V253, P1357

[2] PLASMODIUM-FALCIPARUM - INDUCTION, SELECTION, AND CHARACTERIZATION OF PYRIMETHAMINE-RESISTANT MUTANTS [J].

BANYAL, HS ;

INSELBURG, J .

EXPERIMENTAL PARASITOLOGY, 1986, 62 (01) :61-70

[3] PRIMARY STRUCTURE OF THE GENE ENCODING THE BIFUNCTIONAL DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE OF LEISHMANIA-MAJOR [J].

BEVERLEY, SM ;

ELLENBERGER, TE ;

CORDINGLEY, JS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (08) :2584-2588

[4] AN ANLYSIS OF DEVELOPMENT OF RESISTANCE TO PROGUANIL AND PYRIMETHAMINE IN PLASMODIUM GALLINACEUM [J].

BISHOP, A .

PARASITOLOGY, 1962, 52 (3-4) :495-&

[5]

BOLIN JT, 1982, J BIOL CHEM, V257, P13650

[6] MOLECULAR-CLONING AND SEQUENCE-ANALYSIS OF THE PLASMODIUM-FALCIPARUM DIHYDROFOLATE-REDUCTASE THYMIDYLATE SYNTHASE GENE [J].

BZIK, DJ ;

LI, WB ;

HORII, T ;

INSELBURG, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) :8360-8364

[7]

CHEN GX, 1987, MOL PHARMACOL, V31, P430

[8] ANTIFOLATE DRUG SELECTION RESULTS IN DUPLICATION AND REARRANGEMENT OF CHROMOSOME-7 IN PLASMODIUM-CHABAUDI [J].

COWMAN, AF ;

LEW, AM .

MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (11) :5182-5188

[9] AMINO-ACID CHANGES LINKED TO PYRIMETHAMINE RESISTANCE IN THE DIHYDROFOLATE-REDUCTASE THYMIDYLATE SYNTHASE GENE OF PLASMODIUM-FALCIPARUM [J].

COWMAN, AF ;

MORRY, MJ ;

BIGGS, BA ;

CROSS, GAM ;

FOOTE, SJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (23) :9109-9113

[10] THE MECHANISM OF PYRIMETHAMINE RESISTANCE IN PLASMODIUM-FALCIPARUM [J].

DIECKMANN, A ;

JUNG, A .

PARASITOLOGY, 1986, 93 :275-278

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