Rational design of anticytoadherence inhibitors for Plasmodium falciparum based on the crystal structure of human intercellular adhesion molecule 1
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Rational design of anticytoadherence inhibitors for Plasmodium falciparum based on the crystal structure of human intercellular adhesion molecule 1. / Dormeyer, Matthias; Adams, Yvonne; Kramer, Bernd; Chakravorty, Srabasti; Tse, Man Tsuey; Pegoraro, Stefano; Whittaker, Lisa; Lanzer, Michael; Craig, Alister.
In: Antimicrobial Agents and Chemotherapy, Vol. 50, No. 2, 02.2006, p. 724-730.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rational design of anticytoadherence inhibitors for Plasmodium falciparum based on the crystal structure of human intercellular adhesion molecule 1
AU - Dormeyer, Matthias
AU - Adams, Yvonne
AU - Kramer, Bernd
AU - Chakravorty, Srabasti
AU - Tse, Man Tsuey
AU - Pegoraro, Stefano
AU - Whittaker, Lisa
AU - Lanzer, Michael
AU - Craig, Alister
PY - 2006/2
Y1 - 2006/2
N2 - Adhesion of Plasmodium falciparum-infected erythrocytes (IE) to host endothelium has been associated with pathology in malaria. Although the interaction with endothelial cells can be complex due to the relatively large number of host receptors available for binding, specific proteins have been identified that are more commonly used than others. For example, binding to intercellular adhesion molecule 1 (ICAM 1) is found frequently in parasites from pediatric cases of malaria. The binding site for P. falciparum-infected erythrocytes on ICAM 1 has been mapped in some detail and is distinct from the site for lymphocyte function-associated antigen 1 (LFA-1). Part of the ICAM 1 binding site for P. falciparum-infected erythrocytes (the DE loop) was used to screen a library of compounds based on its structure (derived from the crystal structure of human ICAM 1). This resulted in the identification of 36 structural mimeotopes as potential competitive inhibitors of binding. One of these compounds, (+)-epigalloyl-catechin-gallate [(+)-EGCG], was found to inhibit IE adhesion to ICAM 1 in a dose-dependent manner with two variant ICAM 1-binding parasite lines, providing the first example of a potential mimeotope-based anticytoadherence inhibitor for Plasmodium falciparum.
AB - Adhesion of Plasmodium falciparum-infected erythrocytes (IE) to host endothelium has been associated with pathology in malaria. Although the interaction with endothelial cells can be complex due to the relatively large number of host receptors available for binding, specific proteins have been identified that are more commonly used than others. For example, binding to intercellular adhesion molecule 1 (ICAM 1) is found frequently in parasites from pediatric cases of malaria. The binding site for P. falciparum-infected erythrocytes on ICAM 1 has been mapped in some detail and is distinct from the site for lymphocyte function-associated antigen 1 (LFA-1). Part of the ICAM 1 binding site for P. falciparum-infected erythrocytes (the DE loop) was used to screen a library of compounds based on its structure (derived from the crystal structure of human ICAM 1). This resulted in the identification of 36 structural mimeotopes as potential competitive inhibitors of binding. One of these compounds, (+)-epigalloyl-catechin-gallate [(+)-EGCG], was found to inhibit IE adhesion to ICAM 1 in a dose-dependent manner with two variant ICAM 1-binding parasite lines, providing the first example of a potential mimeotope-based anticytoadherence inhibitor for Plasmodium falciparum.
UR - http://www.scopus.com/inward/record.url?scp=31944441961&partnerID=8YFLogxK
U2 - 10.1128/AAC.50.2.724-730.2006
DO - 10.1128/AAC.50.2.724-730.2006
M3 - Journal article
C2 - 16436732
AN - SCOPUS:31944441961
VL - 50
SP - 724
EP - 730
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 2
ER -
ID: 340559273