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Template-Mediated Biomineralization of Hemozoin

Published online by Cambridge University Press:  10 February 2011

David W. Wright
Affiliation:
Duquesne University, Dept. of Chemistry and Biochemistry, Pittsburgh, Pennsylvania 15282–1530
James Ziegler
Affiliation:
Duquesne University, Dept. of Chemistry and Biochemistry, Pittsburgh, Pennsylvania 15282–1530
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Abstract

A critical target for the development of new antimalarial treatments is the detoxification pathway of free heme released during the catabolism of host hemoglobin in the digestive vacuole of the malaria parasite Plasmodium falciparum. We have synthesized and examined two peptide dendrimers (BNT I and II) based on the tandem repeat motif of HRP II from P. falciparum for their abilities to both bind heme substrates and to form the critical detoxification polymer hemozoin. Each substrate was capable of binding significant amounts of the natural substrate Fe(III)PPIX along with other substrates such as Zn(II)PPIX and the metal free PPIX. Further, it was shown that the dendrimeric BNT I and II were capable of supporting the aggregation of hemozoin and that this process could be inhibited by the known antimalarial drug, chloroquine.

Type
Research Article
Copyright
Copyright © Materials Research Society 2000

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