RESUMO
The α-gal epitope, which refers to the carbohydrate α-d-Galp-(1 â 3)-ß-d-Galp-(1 â 4)-d-GlcNAc-R, was first described in the glycoconjugates of mammals other than humans. Evolution caused a mutation that resulted in the inactivation of the α-1,3-galactosyltransferase gene. For that reason, humans produce antibodies against α-d-Galp containing glycoproteins and glycolipids of other species. We summarize here the glycoconjugates with α-d-Galp structures in Trypanosoma, Leishmania, and Plasmodium pathogenic protozoa. These were identified in infective stages of Trypanosoma cruzi and in Plasmodium sporozoites. In Leishmania, α-d-Galp is linked differently in the glycans of glycoinositolphospholipids (GIPLs). Chemically synthesized neoglycoconjugates have been proposed as diagnostic tools and as antigens for vaccines. Several syntheses reported for the α-gal trisaccharide, also called the Galili epitope, and the glycans of GIPLs found in Leishmania, the preparation of neoglycoconjugates, and the studies in which they were involved are also included in this Review.
Assuntos
Leishmania , Trissacarídeos , Sequência de Carboidratos , Epitopos , Glicoconjugados , Leishmania/genética , Proteínas de ProtozoáriosRESUMO
Trypanosoma cruzi, the protozoa that causes Chagas disease in humans, is transmitted by insects from the Reduviidae family. The parasite has developed the ability to change the structure of the surface molecules, depending on the host. Among them, the mucins are the most abundant glycoproteins. Structural studies have focused on the epimastigotes and metacyclic trypomastigotes that colonize the insect, and on the mammal trypomastigotes. The carbohydrate in the mucins fulfills crucial functions, the most important of which being the accepting of sialic acid from the host, a process catalyzed by the unique parasite trans-sialidase. The sialylation of the parasite influences the immune response on infection. The O-linked sugars have characteristics that differentiate them from human mucins. One of them is the linkage to the polypeptide chain by the hexosamine, GlcNAc, instead of GalNAc. The main monosaccharide in the mucins oligosaccharides is galactose, and this may be present in three configurations. Whereas ß-d-galactopyranose (ß-Galp) was found in the insect and the human stages of Trypanosoma cruzi, ß-d-galactofuranose (ß-Galf) is present only in the mucins of some strains of epimastigotes and α-d-galactopyranose (α-Galp) characterizes the mucins of the bloodstream trypomastigotes. The two last configurations confer high antigenic properties. In this review we discuss the different structures found and we pose the questions that still need investigation on the exchange of the configurations of galactose.
Assuntos
Doença de Chagas/parasitologia , Mucinas , Oligossacarídeos/química , Trypanosoma cruzi , Configuração de Carboidratos , Sequência de Carboidratos , Galactose/química , Interações Hospedeiro-Parasita , Humanos , Mucinas/química , Mucinas/imunologia , Ácido N-Acetilneuramínico/química , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/fisiologiaRESUMO
The trans-sialidase from Trypanosoma cruzi (TcTS), the agent of Chagas' disease, is a unique enzyme involved in mammalian host-cell invasion. Since T. cruzi is unable to synthesize sialic acids de novo, TcTS catalyzes the transfer of alpha-(2-->3)-sialyl residues from the glycoconjugates of the host to terminal beta-galactopyranosyl units present on the surface of the parasite. TcTS also plays a key role in the immunomodulation of the infected host. Chronic Chagas' disease patients elicit TcTS-neutralizing antibodies that are able to inhibit the enzyme. N-Glycolylneuraminic acid has been detected in T. cruzi, and the trans-sialidase was pointed out as the enzyme involved in its incorporation from host glycoconjugates. However, N-glycolylneuraminic acid alpha-(2-->3)-linked-containing oligosaccharides have not been analyzed as donors in the T. cruzi trans-sialidase reaction. In this paper we studied the ability of TcTS to transfer N-glycolylneuraminic acid from Neu5Gc(alpha2-->3)Gal(beta1-->4)GlcbetaOCH(2)CH(2)N(3) (1) and Neu5Gc(alpha2-->3)Gal(beta1-->3)GlcNAcbetaOCH(2)CH(2)N(3) (2) to lactitol, N-acetyllactosamine and lactose as acceptor substrates. Transfer from 1 was more efficient (50-65%) than from 2 (20-30%) for the three acceptors. The reactions were inhibited when the enzyme was preincubated with a neutralizing antibody. K(m) values were calculated for 1 and 2 and compared with 3'-sialyllactose using lactitol as acceptor substrate. Analysis was performed by high-performance anion-exchange (HPAEC) chromatography. A competitive transfer reaction of compound 1 in the presence of 3'-sialyllactose and N-acetyllactosamine showed a better transfer of Neu5Gc than of Neu5Ac.