Rh1 high activity binding peptides inhibit high percentages of Plasmodium falciparum FVO strain invasion

Gabriela Arévalo-Pinzón, Hernando Curtidor, Marina Muñoz, Diana Suarez, Manuel A. Patarroyo, Manuel E. Patarroyo

Resultado de la investigación: Contribución a RevistaArtículo

5 Citas (Scopus)

Resumen

Identifying the minimal functional regions of the proteins which the malaria parasite uses when invading its host cells constitutes the first and most important approach in an effective design for a chemically synthesised, multi-antigen, multi-stage, subunit-based vaccine. This work has been aimed at identifying the PfRh1 protein binding regions (residues 1-2580) belonging to the reticulocyte binding-like (RBL or P. falciparum Rh [PfRh]) family implicated in the parasite's alternative target cell invasion routes. Eighteen peptide regions (called high activity binding peptides - HABPs) binding to red blood cells (RBC) were identified in peptides mapped in a highly robust, specific and sensitive receptor-ligand assay. These HABPs were saturable in the experimental conditions assayed here and most had an alpha helix structure. Polymorphism studies revealed that only six of the eighteen HABPs identified had changes at amino acid level amongst the seven P. falciparum strains evaluated. Most HABPs' specific binding became altered when RBC were treated with neuraminidase, chymotrypsin and trypsin, suggesting differing sensitivity for RBC membrane receptors. After ascertaining that the Rh1 gene was transcribed and expressed in late-stage schizonts of the FCB-2 strain, invasion inhibition assays were carried out. When most of these HABPs were assayed in P. falciparum in vitro culture they were able to inhibit high percentages of FVO strain invasion compared to low inhibition percentages observed with the FCB-2 strain. This data shows small Rh1 regions' participation during invasion and suggests that these units should be included in further immunological and structural studies. © 2013 Elsevier Ltd.
Idioma originalEnglish (US)
Páginas (desde-hasta)1830-1837
Número de páginas8
PublicaciónVaccine
DOI
EstadoPublished - abr 3 2013

Huella dactilar

Plasmodium falciparum
Erythrocytes
peptides
Peptides
erythrocytes
Parasites
Schizonts
Subunit Vaccines
Reticulocytes
Neuraminidase
Protein Binding
parasites
schizonts
reticulocytes
receptors
Malaria
cell invasion
sialidase
protein binding
chymotrypsin

Citar esto

Arévalo-Pinzón, Gabriela ; Curtidor, Hernando ; Muñoz, Marina ; Suarez, Diana ; Patarroyo, Manuel A. ; Patarroyo, Manuel E. / Rh1 high activity binding peptides inhibit high percentages of Plasmodium falciparum FVO strain invasion. En: Vaccine. 2013 ; pp. 1830-1837.
@article{76eb450c1cbe428e8583e81ac5ec3dad,
title = "Rh1 high activity binding peptides inhibit high percentages of Plasmodium falciparum FVO strain invasion",
abstract = "Identifying the minimal functional regions of the proteins which the malaria parasite uses when invading its host cells constitutes the first and most important approach in an effective design for a chemically synthesised, multi-antigen, multi-stage, subunit-based vaccine. This work has been aimed at identifying the PfRh1 protein binding regions (residues 1-2580) belonging to the reticulocyte binding-like (RBL or P. falciparum Rh [PfRh]) family implicated in the parasite's alternative target cell invasion routes. Eighteen peptide regions (called high activity binding peptides - HABPs) binding to red blood cells (RBC) were identified in peptides mapped in a highly robust, specific and sensitive receptor-ligand assay. These HABPs were saturable in the experimental conditions assayed here and most had an alpha helix structure. Polymorphism studies revealed that only six of the eighteen HABPs identified had changes at amino acid level amongst the seven P. falciparum strains evaluated. Most HABPs' specific binding became altered when RBC were treated with neuraminidase, chymotrypsin and trypsin, suggesting differing sensitivity for RBC membrane receptors. After ascertaining that the Rh1 gene was transcribed and expressed in late-stage schizonts of the FCB-2 strain, invasion inhibition assays were carried out. When most of these HABPs were assayed in P. falciparum in vitro culture they were able to inhibit high percentages of FVO strain invasion compared to low inhibition percentages observed with the FCB-2 strain. This data shows small Rh1 regions' participation during invasion and suggests that these units should be included in further immunological and structural studies. {\circledC} 2013 Elsevier Ltd.",
author = "Gabriela Ar{\'e}valo-Pinz{\'o}n and Hernando Curtidor and Marina Mu{\~n}oz and Diana Suarez and Patarroyo, {Manuel A.} and Patarroyo, {Manuel E.}",
year = "2013",
month = "4",
day = "3",
doi = "10.1016/j.vaccine.2013.01.052",
language = "English (US)",
pages = "1830--1837",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",

}

Rh1 high activity binding peptides inhibit high percentages of Plasmodium falciparum FVO strain invasion. / Arévalo-Pinzón, Gabriela; Curtidor, Hernando; Muñoz, Marina; Suarez, Diana; Patarroyo, Manuel A.; Patarroyo, Manuel E.

En: Vaccine, 03.04.2013, p. 1830-1837.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Rh1 high activity binding peptides inhibit high percentages of Plasmodium falciparum FVO strain invasion

AU - Arévalo-Pinzón, Gabriela

AU - Curtidor, Hernando

AU - Muñoz, Marina

AU - Suarez, Diana

AU - Patarroyo, Manuel A.

AU - Patarroyo, Manuel E.

PY - 2013/4/3

Y1 - 2013/4/3

N2 - Identifying the minimal functional regions of the proteins which the malaria parasite uses when invading its host cells constitutes the first and most important approach in an effective design for a chemically synthesised, multi-antigen, multi-stage, subunit-based vaccine. This work has been aimed at identifying the PfRh1 protein binding regions (residues 1-2580) belonging to the reticulocyte binding-like (RBL or P. falciparum Rh [PfRh]) family implicated in the parasite's alternative target cell invasion routes. Eighteen peptide regions (called high activity binding peptides - HABPs) binding to red blood cells (RBC) were identified in peptides mapped in a highly robust, specific and sensitive receptor-ligand assay. These HABPs were saturable in the experimental conditions assayed here and most had an alpha helix structure. Polymorphism studies revealed that only six of the eighteen HABPs identified had changes at amino acid level amongst the seven P. falciparum strains evaluated. Most HABPs' specific binding became altered when RBC were treated with neuraminidase, chymotrypsin and trypsin, suggesting differing sensitivity for RBC membrane receptors. After ascertaining that the Rh1 gene was transcribed and expressed in late-stage schizonts of the FCB-2 strain, invasion inhibition assays were carried out. When most of these HABPs were assayed in P. falciparum in vitro culture they were able to inhibit high percentages of FVO strain invasion compared to low inhibition percentages observed with the FCB-2 strain. This data shows small Rh1 regions' participation during invasion and suggests that these units should be included in further immunological and structural studies. © 2013 Elsevier Ltd.

AB - Identifying the minimal functional regions of the proteins which the malaria parasite uses when invading its host cells constitutes the first and most important approach in an effective design for a chemically synthesised, multi-antigen, multi-stage, subunit-based vaccine. This work has been aimed at identifying the PfRh1 protein binding regions (residues 1-2580) belonging to the reticulocyte binding-like (RBL or P. falciparum Rh [PfRh]) family implicated in the parasite's alternative target cell invasion routes. Eighteen peptide regions (called high activity binding peptides - HABPs) binding to red blood cells (RBC) were identified in peptides mapped in a highly robust, specific and sensitive receptor-ligand assay. These HABPs were saturable in the experimental conditions assayed here and most had an alpha helix structure. Polymorphism studies revealed that only six of the eighteen HABPs identified had changes at amino acid level amongst the seven P. falciparum strains evaluated. Most HABPs' specific binding became altered when RBC were treated with neuraminidase, chymotrypsin and trypsin, suggesting differing sensitivity for RBC membrane receptors. After ascertaining that the Rh1 gene was transcribed and expressed in late-stage schizonts of the FCB-2 strain, invasion inhibition assays were carried out. When most of these HABPs were assayed in P. falciparum in vitro culture they were able to inhibit high percentages of FVO strain invasion compared to low inhibition percentages observed with the FCB-2 strain. This data shows small Rh1 regions' participation during invasion and suggests that these units should be included in further immunological and structural studies. © 2013 Elsevier Ltd.

U2 - 10.1016/j.vaccine.2013.01.052

DO - 10.1016/j.vaccine.2013.01.052

M3 - Article

SP - 1830

EP - 1837

JO - Vaccine

JF - Vaccine

SN - 0264-410X

ER -