Plasmodium falciparum: Carbohydrates as receptor sites of invasion

• Published in: Experimental parasitology Vol. 58; no. 3; pp. 290 - 306
• Main Authors: Hermentin, P., Paulsen, H., Kolar, C., Enders, B.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.12.1984; Elsevier
• Subjects: 3- O-Me-DGlc 3- O-methyl- d-glucose; 3- O-Me-α, β-DGlcOMe, methyl α,β- d-glucopyranoside; Animals; Antigen T; Biological and medical sciences; Blood Group Antigens; Carbohydrate Metabolism; Carbohydrates - pharmacology; Chitobiose; Cultivation; DGal d-galactose; DGalNAc N-acetyl- d-galactosamine; DGlc d-glucose; DGlcNAc N-acetyl- d-glucosamine; Disaccharides - pharmacology; DMan d-mannose; Erythrocytes - parasitology; Fundamental and applied biological sciences. Psychology; Glycophorin; Haptens; Human protozoal diseases; Humans; Infectious diseases; Invasion inhibitors; LFuc l-fucose; Life cycle. Host-agent relationship. Pathogenesis; Malaria; Malaria human; Medical sciences; Methylglycosides - pharmacology; Monosaccharides - pharmacology; N-acetyl- d-galactosamine; N-acetyl- d-glucosamine; NeuAc N-acetylneuraminic acid; Parasitic diseases; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - growth & development; Plasmodium falciparum - metabolism; Protozoa; Protozoa parasitic; Protozoal diseases; Sialoglycoprotein; Sugar chain complex-type carbohydrates; Trisaccharides - pharmacology; Tropical medicine; α,βDGalNAcOMe, methyl 2-acetamido-2-deoxy- α,β- d-gal-actopyranoside; α,βDGalOMe, methyl α,β- d-galactopyranoside; α,βDGlcNAcOMe, methyl 2-acetamido-2-deoxy- α,β- d-glucopyranoside; α,βDGlcOMe, methyl α,β- d-glucopyranoside; α,βLFucOMe, methyl α,β- l-fucopyranoside; α,βNeuAcOMe, α,β-methylglycoside of N-acetylneuraminic acid; αDGlcOPhNO 2, p-aminophenyl α- d-glucopyranoside; αDManOMe, methyl α- d-mannopyranoside; βDGlcNAcOPhNO 2, p-aminophenyl 2-acetamido-2-deoxy-β- d-glucopyranoside; βDGlcNAcOPhNO 2, p-aminophenyl 2-acetamido-2-deoxy-β- d-glucopyranoside; Invasion inhibitors; α,βDGalOMe, methyl α,β- d-galactopyranoside; N-acetyl- d-glucosamine; α,βDGlcOMe, methyl α,β- d-glucopyranoside; Protozoa parasitic; DGlcNAc N-acetyl- d-glucosamine; α,βDGalNAcOMe, methyl 2-acetamido-2-deoxy- α,β- d-gal-actopyranoside; Chitobiose; Plasmodium falciparum; BSA; αDGlcOPhNO 2, p-aminophenyl α- d-glucopyranoside; RBC; Sialoglycoprotein; α,βLFucOMe, methyl α,β- l-fucopyranoside; αDManOMe, methyl α- d-mannopyranoside; 3- O-Me-DGlc 3- O-methyl- d-glucose; Cultivation; Malaria human; N-acetyl- d-galactosamine; DGal d-galactose; DMan d-mannose; DGlc d-glucose; α,βDGlcNAcOMe, methyl 2-acetamido-2-deoxy- α,β- d-glucopyranoside; α,βNeuAcOMe, α,β-methylglycoside of N-acetylneuraminic acid; DGalNAc N-acetyl- d-galactosamine; NeuAc N-acetylneuraminic acid; PE; Glycophorin; Sugar chain complex-type carbohydrates; 3- O-Me-α, β-DGlcOMe, methyl α,β- d-glucopyranoside; Antigen T; LFuc l-fucose; Protozoa; Growth; Carbohydrate; Inhibition; Pathogen; In vitro; Biological receptor
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/0014-4894(84)90046-8

Monosaccharides, disaccharides, and trisaccharides were tested as inhibitors of the in vitro growth of Plasmodium falciparum (strain FCB). While certain monosaccharides ( N-acetyl- d-glucosamine, d-mannose, and 3- O-methyl- d-glucose) proved to exhibit a toxic or reversibly retarding effect on the intraerythrocytic development of the parasite, the corresponding α- or β-methylglycosides did not. Several methylglycosides, synthetic di- and tri-saccharides, and artificial blood group antigens were further tested for inhibitory effects on invasion of host red blood cells in vitro. The synthetic disaccharides βDGlcNAc(1 → 4) α DManOMe and βDGlcNAc(1 → 4) DGlcNAc (chitobiose) were good inhibitors of invasion at 10 m M concentration, whereas βDGal(1 → 4)βDGlcNAcOMe was negligibly inhibitory. The inhibition rate of N-acetyl- d-glucosamine, β-glycosidically linked to bovine serum albumin (BSA) by an alipathic spacer, (CH 2) 8CO, was not enhanced, compared to the corresponding hapten, βDGlcNAcO(CH 2) 8COOCH 3. The inhibition rates of blood group A-and B-trisaccharide haptens, which were inhibitors of invasion, were also not significantly enhanced when coupled to BSA by way of the corresponding amide spacer, (CH 2) 2NHCO(CH 2) 7CO. A remarkable enhancement of the inhibition rate was, however, observed when βDGal(1 → 3) αDGalNAcO(CH 2) 2NHCO(CH 2) 7COOCH 3 (T-hapten) was coupled to BSA. A clear-cut decrease in the inhibition rates of different β-glycosides of N-acetyl- d-glucosamine, βDGlcNAcOR, was observed, depending on the nature of the aglycon R( p-nitrophenyl > (CH 2) 8COOCH 3 > (CH 2) 2NHCO(CH 2) 2COOCH 3 > CH 3). Also, p-nitrophenyl-α- d-glucopyranoside was a much better inhibitor of invasion than the corresponding methyl glycoside, αDGlcOMe, which was not inhibitory. The properties of the aglycon spacer, used for the covalent attachment of the carbohydrate to the carrier protein, may thus be crucial for the outcome of the inhibition rate.