Primary Structure of the Glycans from Human Lactotransferrin

Abstract

The polypeptide chain of human lactotransferrin possesses two glycosylation sites to which glycans are linked through an N-(P-asparty1)-N-acetylglucosaminylamine bond and which are structurally heterogenous. After chymotryptic or pronase digestions, glycopeptides with five different glycan structures could be isolated. For three of them, the structure has been determined by the application of methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, enzymatic cleavage and 'H-NMR spectroscopy at 360 MHz: Glycopeptides A and B : NeuAc(cr2-6)Gal(~1-4)GlcNAc(~l-2)Man(crl-3) shows that important differences exist between the number and the structure of the glycans present in these four kinds of transferrins.In the case of human lactotransferrin, in 1966, the presence of two glycans linked by a 4-N-(2-acetamido-2-deoxy-B-~-glucopyranosy1)-L-asparagine linkage was described as well as one 0-glycosidically-linked glycan [17]. The presence of two N-glycosidically-linked glycans was confirmed in 1973 and for one of them the structure was proposed [18].Microheterogeneity of the carbohydrate moieties was later demonstrated and partial results concerning different glycan structures were given in general reviews [19-211. In the present paper we describe the complete primary structure of three types of glycans as determined by methanolysis, methylation analysis, hydrazinolysis/nitrous deamination, mass spectrometry, enzymatic cleavage and 'H-NMR spectroscopy at [111._.___

The role and potential of sialic acid in human nutrition

“…Because casein synthesis is not initiated in the first few days of lactation (Kunz & Lönnerdal, 1990), whey proteins make the largest contribution to total protein at the beginning of lactation, particularly secretory IgA (which contains 12% carbohydrate) and lactoferrin (6% carbohydrate) (Kunz & Lönnerdal, 1990;Rudloff & Kunz, 1997). The carbohydrate side chains of human lactoferrin consist of an N-acetyl-lactosamine glycan with sialic acid in the terminal position (Spik et al, 1982). Cow's milk, however, is low in lactoferrin and the glycan side chains show pronounced differences to human lactoferrin.…”

The N‐terminal domain I of human lactotransferrin binds specifically to phytohemagglutinin‐stimulated peripheral blood human lymphocyte receptors

“…However, these glycoproteins differ in the number, the structure and the location of their glycans [9][10][11][12]. Otherwise, these transferrins bind to different cells such as reticulocytes (serotransferrin) [131, enterocytes (lactotransferrin) [14,15] and chick embryo red blood cells (ovotransferrin) [16], thus suggesting that specific transferrin receptors are present at the surface of these cells and recognize a glycan, a peculiar region of the polypeptide chain, or both.…”

Lactotransferrin binding to its platelet receptor inhibits platelet aggregation

“…Major progress has been made in the determination of its glycan [6] and peptide [7,8] sequences, three-dimensional structure and the understanding of iron capture [9, 101. In contrast, little is known about either its biological activity or target cells.…”

“…Lactotransfemn (also called lactoferrin), discovered by Montreuil et al in human milk [l, 21 was also found in human granulocytes [3] and numerous epithelial secretions [4, 51. Major progress has been made in the determination of its glycan [6] and peptide [7,8] sequences, three-dimensional structure and the understanding of iron capture [9, 101. In contrast, little is known about either its biological activity or target cells.…”