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Loci and motifs of the GalNAcα1 → 3/O related glycotopes in the mammalian glycoconjugates and their lectin recognition roles

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Abstract

Galα1 → and GalNAcα1 → are the two essential key sugars in human blood group AB active glycotopes, in which GalNAcα1 → related sequences are located at both sides of the nonreducing and the reducing ends of human blood group A active O-glycans. It is also found at the nonreducing ends of GlcNAc N-glycans and glycosphingolipid(GSL) of human blood group A active glycotopes (Ah) and Forssman antigen (Fp). When monosaccharides and their α, β anomers are involved in basic units to express the complex size of the combining sites of the GalNAcα1 → specific lectins, they can be divided into a cavity site to accommodate the GalNAcα → key sugar and a subsite with a wide and broad range of recognition area to adopt the rest part of sugar sequences or glycotopes. The function of the subsite is assumed to act as an enhancement factor to increase its affinity power. The following three points are the theme of this mini review: (1) the loci and distribution of the GalNAcα1 → related glycotopes in mammalian glycoconjugates are illustrated and their chemical structures are advanced by the expression of the disaccharide units and code system; (2) the sizes and motifs of GalNAcα1 → specific lectin-glycan interactions are given and (3) the role of the polyvalent blood group Ah and Bh glycotopes as blood group AB antigens are proposed. These three highlights should provide an essential background required for the advances in this field.

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Abbreviations

Key sugar, and glycotopes:

Sia, Neu5Ac, SA, Sialic acid; Except LFuc or Fuc, all other monosaccharides (Gal, Glc, Man-GalNAc, GlcNAc and Sia) in glycoconjugates in DForms; Lea, b, x, y, Lea, Leb, Lex, Ley; sLea, Sialyl Lea and Sialyl Leb

Glyco structural units/code system:

A, GalNAcα1→3Gal; Ah, GalNAcα1→3(LFucα1-2)Gal; B, Galα1→3Gal; Bh, Galα1→3(LFucα1-2)Gal; H, LFucα1→2(Gal); h, crypto form of H; Tn, GalNAcα1→Ser/Thr; Tα, Core 1, Type III precursor sequence, Galβ1→3GalNAcα→Ser/Thr; C, chitin disaccharide, GlcNAcβ1→4GlcNAcβ; Cf, GlcNAcβ1→4(LFucα1→6)GlcNAcβ; More in Table 1

Glycoproteins (gps):

HOC, human cyst gps: glycoproteins isolated from human ovarian cyst fluid; OSM, ovine submandibular mucin (glycoprotein)

Lectins:

GBP(CBP), Glycan (Carbohydrate) binding Protein; DBA, Dolichos biflorus agglutinin; ABA, Agaricus bisporus agglutinin; GSI-A4, Bandeiraea (Griffonia) simplicifolia lectin-I, isolectin A4; VVL-B4, Vicia villosa B4; More in Tables 2 and 3

ELLSA and ELLSIA:

Enzyme-linked lectinosorbent assay and inhibition assay; RF, Recognition Factor

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Acknowledgements

This work was supported by CGU research grant, BMRP 008, BMRP 530, and MICCs Forever Fund (in process), Kwei-San, Tao-yuan, Taiwan. The author would like to thanks Drs. Khoo KH and Yu S. Y. for their long term contributions in the field of glycan structural identification, Professor Simon Silver manuscript preparation, and Ms. Ko’s typing assistance.

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  1. Glycome Research Laboratory, Institute of Molecular and Cellular Biology, College of Medicine, Chang-Gung University, Tao-yuan, 33302, Taiwan

    Albert M. Wu

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The review is dedicated to the late S. Hakomori (Pacific Northwest Research Institute, Seattle), E. A. Kabat (Columbia Medical Center, New York) and W. M. Watkins (Imperial College School of Medicine, London). During the past seventy years, they made great pioneer contributions to the field of glycoconjugates.

This article is part of the Topical Collection on Tribute to Professor Sen-itiroh Hakomori

Guest Editors: Alessandro Prinetti, Kazuhisa Iwabuchi, Subhash Basu

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Wu, A.M. Loci and motifs of the GalNAcα1 → 3/O related glycotopes in the mammalian glycoconjugates and their lectin recognition roles. Glycoconj J 39, 633–651 (2022). https://doi.org/10.1007/s10719-022-10068-6

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