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The structure of nephritogenoside. A nephritogenic glycopeptide with alpha-N-glycosidic linkage.

1988; Elsevier BV; Volume: 263; Issue: 25 Linguagem: Inglês

10.1016/s0021-9258(18)37780-9

1083-351X

S. Shibata, Tadahiro Takeda, Y Natori,

Enzyme Catalysis and Immobilization

Nephritogenoside is a glycopeptide with the ability to induce chronic progressive glomerulonephritis (end stage kidney) in homologous animals, by a single footpad injection.This substance contains a novel carbohydrate-peptide linkage, Le. the trisaccharide (3 glucose residues) chain is a-N-glycosidically linked to the polypeptide chain through the amido nitrogen of an asparagine residue at the N-terminal.It was found that the peptide portion of nephritogenoside is composed of twenty-one amino acids (Asnl-Pro-Leu-Phe-Gly6-Ile-Ala-Gly-Glu-Asp'o-G1y-Pro-Thr-Gly-Pro'6-Ser-Gly-Ile-Val-Gly20-Gln21) and that the peptide portion has a repeated Gly-X-Y structure.Nephritogenoside is a glycopeptide isolated as a minor component in the basement membrane of normal animals (1).This substance was designated nephritogenoside because it is a glycoside with the ability to induce glomerulonephritis in homologous animals (2).This finding has been confirmed by Nishii et al. (3).However, isolation and purification of this compound has, in general, been very difficult, because only 5-6 mg of nephritogenoside is isolated and purified from the perfused renal cortices of 1200 normal rats, after a preparation period lasting more than 3 months.Thus, the report of Nishii (3) may be the one with a scarcity value.We have demonstrated that the biologically active portion of nephritogenoside is in the sugar moiety and that the receptor for concanavalin A present in normal rat glomerular basement membranes can be identified as nephritogenoside, which is located in the inner layer (lamina rara interna) of the glomerular capillary loop (1).From methylation analysis (4), the concanavalin A test (l), and studies of I3C NMR data (5, 21), in 1980, we proposed the following structure for nephritogenoside: Glc(a1 + 6) Glc(P1-6)Glc(al+ N)-peptide.The peptide portion of nephritogenoside is directly and a- N-glycosidically bonded to the trisaccharide portion (4,5,21).The proposed structure was supported by the successful production of synthetic compounds with nephritogenic activity (6, 7).However, it has long been difficult to determine the amino acid sequence of nephritogenoside and site of carbohydrate attachment in the glycopeptide.We have recently found the reason for this difficulty, based on evidence that the carbohydrate chain of nephritogenoside binds directly with the Nterminal amino acid of the peptide portion.In this paper, we