ANTIMALARIAL ACTIVITIES OF OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES IN CHLOROQUINE-RESISTANT PLASMODIUM-FALCIPARUM

被引：50

作者：

RAPAPORT, E ^{[1
]}

MISIURA, K ^{[1
]}

AGRAWAL, S ^{[1
]}

ZAMECNIK, P ^{[1
]}

机构：

[1] HYBRIDON INC,WORCESTER,MA 01605

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1992年 / 89卷 / 18期

关键词：

MALARIA; DRUG RESISTANCE; MODIFIED OLIGODEOXYNUCLEOTIDES; ANTISENSE;

D O I：

10.1073/pnas.89.18.8577

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Synthetic oligonucleotides and their chemical modifications have been shown to inhibit viral and cellular gene expression by sequence-specific antisense hybridization to target mRNAs. We now report that oligodeoxynucleotide phosphorothioates and their nuclease-resistant modifications are effective in micromolar and submicromolar concentrations against the growth of both chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum in vitro. Parasitized human erythrocytes were found to be accessible to radioactively labeled oligodeoxynucleotides, whereas the uninfected erythrocytes did not permit any cellular entry of the same compounds. The dihydrofolate reductase-thymidylate synthase gene of P. falciparum was demonstrated to be a good target for sequence-dependent inhibition of plasmodial growth by exogenously administered modified oligonucleotides. The antimalarial activities observed in vitro were identical for chloroquine-sensitive and chloroquine-resistant strains of P. falciparum. The antimalarial activity of oligodeoxynucleotide phosphorothioates is related to sequence complementarity to certain regions of the plasmodial genome as well as to non-sequence-defined activities.

引用

页码：8577 / 8580

页数：4

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