Synthesis of type 2 human blood-group antigenic determinants. The H, X, and Y haptens and variations of the H type 2 determinant as probes for the combining site of the lectin I of Ulex europaeus

Abstract

Chemical syntheses of the human blood-group antigenic determinants derived from N-acetyllactosamine are described; namely, the H type 2 [α lFuc(1→2)β dGal(1→4)β dGlcNAc], X [β dGal(1→4)[α lFuc(1→3)]β dGlcNAc], and Y [α lFuc(1→2)β dGal(1→4)[α lFuc(1→3)β dGlcNAc] determinants as glycosides of 8-carboxymethyloctanol. In order to study the binding of the H type 2 determinant with the lectin I of Ulex europaeus, structures designed to specifically alter the hydrophilic and hydrophobic portions of the H type 2 determinant were also prepared; anmely, the 6-deoxy derivative, the 4′-epimer, and the 5″- nor-homolog. The use of these structures, together with the H type 1 hapten and the N-deacetylated forms of both the H type 1 and H type 2 determinants, as inhibitors of the agglutination of O red cells by the lectin allowed the conclusion that the binding of the H type 2 determinant is hydrophobic; the binding involves a wedge-like portion of the determinant that is basically hydrophobic, except for the 5-hydroxymethyl group, which is at the tip of the wedge and forms an intramolecular hydrogen-bond with O-5 for acceptance by a hydrophobic cleft at the surface of the lectin. Blocking procedures involving alkoxymethyl groups and new experiences involving glycosylation reactions are described.