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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
Antimalarial activity of granzyme B and its targeted delivery by a granzyme B-single-chain Fv fusion protein
Stephanie Kapelski1, Melanie de Almeida1, Rainer Fischer1
1Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Pharmaceutical Product Development, Aachen, Germany RWTH Aachen University, Institute for Molecular Biotechnology, Aachen, Germany.
Abstract:
We present here the first evidence that granzyme B acts against Plasmodium falciparum (50% inhibitory concentration [IC50], 1,590 nM; 95% confidence interval [95% CI], 1,197 to 2,112 nM). We created a novel antimalarial fusion protein consisting of granzyme B fused to a merozoite surface protein 4 (MSP4)-specific single-chain Fv protein (scFv), which targets the enzyme to infected erythrocytes, with up to an 8-fold reduction in the IC50 (176 nM; 95% CI, 154 to 202 nM). This study confirms the therapeutic efficacies of recombinant antibody-mediated antimalarial immunotherapeutics based on granzyme B.
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