Non-sequence-specific antimalarial activity of oligodeoxynucleotides
Identifieur interne : 001969 ( Istex/Checkpoint ); précédent : 001968; suivant : 001970Non-sequence-specific antimalarial activity of oligodeoxynucleotides
Auteurs : Diana L. Clark [États-Unis] ; Linda A. Chrisey [États-Unis] ; James R. Campbell [États-Unis, Égypte] ; Eugene A. Davidson [États-Unis]Source :
- Molecular & Biochemical Parasitology [ 0166-6851 ] ; 1994.
English descriptors
- Teeft :
- Antimalarial, Antimalarial activity, Antimalarial effect, Antisense, Assay conditions, Biochemical parasitology, Cerebral malaria, Culture medium, Erythrocyte, Falciparum, Falciparum parasitemia, Falciparum strains, Georgetown university, Host cell, Invasion assay, Negative controls, Nonsense odns, Nucleic acids, Odns, Oligo software, Oligodeoxynucleotides, Oligomers, Parasite, Parasite maturation, Parasite proliferation, Parasitemia, Parasitology, Phosphorothioate, Phosphorothioate oligodeoxynucleotides, Sham synthesis reaction, Sodium salt, Sorbitol treatment, Test cultures.
Abstract
Abstract: The effects of exogenously applied oligodeoxynucleotides on Plasmodium falciparum proliferation was investigated. A fluorescence-activated cell sorter assay was employed to measure parasitemia after administration of either phosphodiester or phosphorothioate oligodeoxynucleotides. We report sequence-independent antimalarial activity preferentially with phosphorothioate congeners with IC50 values in the 1–2 μM range. Phosphorothioate oligodeoxynucleotides which were antisense, sense or nonsense to Plasmodium mRNA, as well as homopolymers (30-mers containing all A or T bases) were equally effective inhibitors of parasitemia. The antimalarial activity was dependent upon oligomer length, concentration, and time of addition to the cultures but was independent of the parasite strain tested. Four P. falciparum strains, including a multi-drug-resistant strain (MDR-K), a drug-sensitive strain (FCR-3), a erythrocyte membrane sialic acid-independent strain (7G8) and a strain isolated from a cerebral malaria patient (CM-87) were equally susceptible to treatment with a phosphorothioate oligomer. Inhibition of red cell invasion is primarily responsible for the observed decrease in proliferation as determined by a study of parasite maturation in the presence of a 30-mer nonsense phosphorothioate oligodeoxynucleotide.
Url:
DOI: 10.1016/0166-6851(94)90015-9
Affiliations:
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A fluorescence-activated cell sorter assay was employed to measure parasitemia after administration of either phosphodiester or phosphorothioate oligodeoxynucleotides. We report sequence-independent antimalarial activity preferentially with phosphorothioate congeners with IC50 values in the 1–2 μM range. Phosphorothioate oligodeoxynucleotides which were antisense, sense or nonsense to Plasmodium mRNA, as well as homopolymers (30-mers containing all A or T bases) were equally effective inhibitors of parasitemia. The antimalarial activity was dependent upon oligomer length, concentration, and time of addition to the cultures but was independent of the parasite strain tested. Four P. falciparum strains, including a multi-drug-resistant strain (MDR-K), a drug-sensitive strain (FCR-3), a erythrocyte membrane sialic acid-independent strain (7G8) and a strain isolated from a cerebral malaria patient (CM-87) were equally susceptible to treatment with a phosphorothioate oligomer. Inhibition of red cell invasion is primarily responsible for the observed decrease in proliferation as determined by a study of parasite maturation in the presence of a 30-mer nonsense phosphorothioate oligodeoxynucleotide.</div></front></TEI><affiliations><list><country><li>Égypte</li><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Clark, Diana L" sort="Clark, Diana L" uniqKey="Clark D" first="Diana L." last="Clark">Diana L. Clark</name></noRegion><name sortKey="Campbell, James R" sort="Campbell, James R" uniqKey="Campbell J" first="James R." last="Campbell">James R. Campbell</name><name sortKey="Chrisey, Linda A" sort="Chrisey, Linda A" uniqKey="Chrisey L" first="Linda A." last="Chrisey">Linda A. Chrisey</name><name sortKey="Davidson, Eugene A" sort="Davidson, Eugene A" uniqKey="Davidson E" first="Eugene A." last="Davidson">Eugene A. Davidson</name></country><country name="Égypte"><noRegion><name sortKey="Campbell, James R" sort="Campbell, James R" uniqKey="Campbell J" first="James R." last="Campbell">James R. Campbell</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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