Abstract
Synthetic peptides patterned on the amino acid sequences found in two exofacial regions of band 3 protein (residues 824-829 of loop 7 and residues 547-553 of loop 3) blocked, in a dose-dependent fashion, the in vitro adherence of Plasmodium falciparum-infected erythrocytes to C32 amelanotic melanoma cells. Intravenous infusion of these synthetic peptides into Aotus and Saimiri monkeys infected with sequestering isolates of P. falciparum resulted in the appearance of mature forms of the parasite in the peripheral circulation. The finding that the peptides were effective as adhesion blockers in the micromolar range suggests that cerebral malaria could be managed through antiadhesion therapy.
MeSH Terms
Amino Acid Sequence
Animals
Anion Exchange Protein 1, Erythrocyte/chemistry,metabolism
Binding, Competitive
Cell Adhesion/drug effects
Erythrocytes/parasitology
Molecular Sequence Data
Peptides/chemistry,metabolism
Plasmodium falciparum/growth & development
Protein Structure, Secondary
Structure-Activity Relationship
Chemicals
Anion Exchange Protein 1, Erythrocyte
Peptides
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Crandall I
Department of Biology, University of California, Riverside 92521.
Collins W E
Gysin J
Sherman I W
References (24)
24 references, click to expand
-
Plasmodium falciparum (human malaria)-induced modifications in human erythrocyte band 3 protein.
Parasitology. 1991 Jun;102 Pt 3:335-40
PMID: 1714069
-
Localization of senescent cell antigen on band 3.
Proc Natl Acad Sci U S A. 1984 Sep;81(18):5753-7
PMID: 6207531
-
Membrane proteins related to anion permeability of human red blood cells. I. Localization of disulfonic stilbene binding sites in proteins involved in permeation.
J Membr Biol. 1974;15(3):207-26
PMID: 4838037
-
Transmission of Plasmodium fragile to Aotus trivirgatus monkeys.
J Parasitol. 1974 Aug;60(4):719-20
PMID: 4212480
-
Human malaria parasites in continuous culture.
Science. 1976 Aug 20;193(4254):673-5
PMID: 781840
-
Anion transport across the erythrocyte membrane, in situ proteolysis of band 3 protein, and cross-linking of proteolytic fragments by 4,4'-diisothiocyano dihydrostilbene-2,2'-disulfonate.
Biochim Biophys Acta. 1979 Jul 5;554(2):498-519
PMID: 486455
-
The carboxyl-terminal domain of human erythrocyte band 3. Description, isolation, and location in the bilayer.
J Biol Chem. 1981 Jun 25;256(12):6463-8
PMID: 7240219
-
Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence.
Nature. 1985 Nov 7-13;318(6041):64-6
PMID: 2414670
-
Expression of senescent antigen on erythrocytes infected with a knobby variant of the human malaria parasite Plasmodium falciparum.
Proc Natl Acad Sci U S A. 1987 Apr;84(7):1931-5
PMID: 3550802
-
Plasmodium falciparum: the behavior of clinical isolates in an in vitro model of infected red blood cell sequestration.
Exp Parasitol. 1988 Apr;65(2):202-8
PMID: 3280334
-
Characterization of a modified red cell membrane protein expressed on erythrocytes infected with the human malaria parasite Plasmodium falciparum: possible role as a cytoadherent mediating protein.
J Cell Biol. 1989 Jan;108(1):23-30
PMID: 2642911
-
The complete amino acid sequence of the human erythrocyte membrane anion-transport protein deduced from the cDNA sequence.
Biochem J. 1988 Dec 15;256(3):703-12
PMID: 3223947
-
Major proteolytic fragments of the murine band 3 protein as obtained after in situ proteolysis.
Biochim Biophys Acta. 1989 Apr 28;980(3):291-8
PMID: 2713407
-
Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum.
Nature. 1989 Sep 7;341(6237):57-9
PMID: 2475784
-
In vitro cytoadherence of Plasmodium falciparum-infected erythrocytes to melanoma cells: factors affecting adhesion.
Parasitology. 1989 Jun;98 Pt 3:359-69
PMID: 2671875
-
Cloning and characterization of band 3, the human erythrocyte anion-exchange protein (AE1).
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9089-93
PMID: 2594752
-
Definition of a physiologic aging autoantigen by using synthetic peptides of membrane protein band 3: localization of the active antigenic sites.
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5734-8
PMID: 1696010
-
Surface molecules on Plasmodium falciparum-infected erythrocytes involved in adherence.
Am J Trop Med Hyg. 1990 Aug;43(2 Pt 2):15-29
PMID: 2202225
-
The pathology of human cerebral malaria.
Am J Trop Med Hyg. 1990 Aug;43(2 Pt 2):30-7
PMID: 2202227
-
Functional characterization of the antibody-mediated protection against blood stages of Plasmodium falciparum in the monkey Saimiri sciureus.
Eur J Immunol. 1990 Oct;20(10):2317-23
PMID: 2242760
-
Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies.
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3175-9
PMID: 1707534
-
Falciparum malaria-infected erythrocytes specifically bind to cultured human endothelial cells.
Science. 1981 Jul 31;213(4507):555-7
PMID: 7017935
-
Parasite sequestration in Plasmodium falciparum malaria: spleen and antibody modulation of cytoadherence of infected erythrocytes.
Proc Natl Acad Sci U S A. 1983 Aug;80(16):5075-9
PMID: 6348780
-
Plasmodium falciparum: the effect of pH and Ca2+ concentration on the in vitro cytoadherence of infected erythrocytes to amelanotic melanoma cells.
Exp Parasitol. 1991 Oct;73(3):362-8
PMID: 1915750