Hemozoin templates

Fig. (3). Hemozoin Production Mediated by Bionucleating Templates. Representative polymerization assay with 50 pM of hemin in 2 ml acetate buffer (500 mM, pH 4.8) at 37° C. BNTI and BNTII were used in 1 and 2 nmol amounts. Chloroquine (CQ, 100 pM) was included with BNT I and BNT n in inhibition reactions. Polyhistidine and bovine serum albumin in approximately 1 and 2 nmol amounts were used in protein control experiments. The blank control was the acetate buffer above. Base line amounts of insoluble aggregate are consistent with those previously reported under similar conditions.

I would like to thank my students who have played a crucial part in the rapid progress that we have made on the role of template-mediated synthesis of hemozoin. I would also like to thank Professor D. Scott Bohle for providing a preprint of the most recent powder diffraction model of hemozoin and for reading sections of this manuscript prior to submission. Without his assistance and cooperation, this review would have been instantly out of date. I would also like to thank the Research Corporation, the Hunkele Charitable Trust of Pittsburgh, the National Foundation of Infectious Diseases, and Duquesne University for financial support of this work. 

Figure 2 Modes of hemozoin inhibition. On a neutrai iipid dropiet tempiate (T), heme can aggregate to form the biomineral HZ. Antimalarials may inhibit this aggregation by binding heme substrate, interacting with the iipid tempiate or trapping heme bound to the template. All actions serve to prevent the formation of HZ.

Biomimetic processes other than inorganic crystallisation have also been described. Wright and co-workers templated the production of the polymer hemozoin, a crystalline heme aggregate used by malarial parasites in a detoxification process. Understanding and controlling this could lead to new antimalarial drugs. Peptide dendrimers containing multiple repeats of the Ala-His-His sequence known to mediate hemozoin formation were prepared and indeed were shown to induce its production. ... 

Figure 4 a) Hemozoin aggregation mediated by bionucleating templates b) pH dependence of the heme aggregation c) SEM and d) XRD characterization of... 

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