Targeting malaria with polyamines |
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Authors: | Geall Andrew J Baugh John A Loyevsky Mark Gordeuk Victor R Al-Abed Yousef Bucala Richard |
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Affiliation: | Vical Inc., 10390 Pacific Center Court, San Diego, California 92121, USA. ageall@vical.com |
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Abstract: | During the asexual cycle of Plasmodium falciparum within the host erythrocyte, the parasite induces a stage-dependent elevation in the levels of polyamines by increased metabolism and uptake of extracellular pools. Polyamine amides of N-methylanthranilic acid have been synthesized which have embedded within them putrescine, spermidine, or spermine and from a charge perspective mimic natural polyamines. The interaction of these polyamine conjugates with human erythrocytes infected with malaria is described using fluorescent microscopy. The fluorescent spermine mimic was the only probe to show measurable intracellular accumulation. This was observed in late stage development but not in the ring stages or in uninfected erythrocytes. |
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