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Disruption of rosetting in Plasmodium falciparum malaria with chemically modified heparin and low molecular weight derivatives possessing reduced anticoagulant and other serine protease inhibition activities

Skidmore, M. A., Dumax-Vorzet, A. F., Guimond, S. E., Rudd, T. R., Edwards, E. A., Turnbull, J. E., Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164 and Yates, E. A. (2008) 'Disruption of rosetting in Plasmodium falciparum malaria with chemically modified heparin and low molecular weight derivatives possessing reduced anticoagulant and other serine protease inhibition activities'. Journal of Medicinal Chemistry, Vol 51, Issue 5, pp. 1453-1458.

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Abstract

Severe malaria has been, in part, associated with the ability of parasite infected red blood cells to aggregate together with uninfected erythrocytes to form rosettes via the parasite protein PfEMP-1. In this study, inhibitors of rosetting by the Plasmodium falciparum strain R-29, based on chemically modified heparin polysaccharides (IC50 = 1.97 x 10(-2) and 3.05 x 10(-3) mg center dot mL(-1)) and their depolymerized, low molecular weight derivatives were identified with reduced anticoagulant and protease (renin, pepsin, and cathepsin-D) activities. Low molecular weight derivatives of the two most effective inhibitors were shown to have distinct minimum size and strain-specific structural requirements for rosette disruption. These also formed distinct complexes in solution when bound to platelet-factor IV.

Item Type: Article
Uncontrolled Keywords: solubilized immune-complexes membrane protein-1 pfemp1 induced thrombocytopenia substitution pattern glucosamine residues human-erythrocytes cr-1 receptors cation-binding factor xa sequences
Subjects: WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
QX Parasitology > Protozoa > QX 135 Plasmodia
QV Pharmacology > QV 38 Drug action.
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1021/jm701337t
Depositing User: Mary Creegan
Date Deposited: 16 Mar 2010 12:10
Last Modified: 06 Feb 2018 13:00
URI: https://archive.lstmed.ac.uk/id/eprint/922

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