Effect of polyvalencies of glycotopes on the binding of a lectin from the edible mushroom, Agaricus bisporus

摘要

piAgaricus bisporus/i agglutinin (ABA) isolated from edible mushroom has a potent anti-proliferative effect on malignant colon cells with considerable therapeutic potential as an anti-neoplastic agent. Since previous studies on the structural requirement for binding were limited to molecular or submolecular levels of Galβ1-3GalNAc (bT/b; Thomsen–Friedenreich disaccharide glycotope; where Gal represents d-galactopyranose and GalNAc represents 2-acetamido-2-deoxy-d-galactopyranose) and its derivatives, the binding properties of ABA were further investigated using our collection of glycans by enzyme-linked lectinosorbent assay and lectin–glycan inhibition assay. The results indicate that polyvalent Galβ1-related glycotopes, GalNAcα1-Ser/Thr (bTn/b), and their cryptoforms, are the most potent factor for ABA binding. They were up to 5.5×10sup5/sup and 4.7×10sup6/sup times more active than monomeric bT/b and GalNAc respectively. The affinity of ABA for ligands can be ranked as: multivalent bT/bsubα/sub (Galβ1-3GalNAcα1-), bTn/b and bI/b/bII/b (Galβ1-3GlcNac/Galβ1-4GlcNAc, where GlcNAc represents 2-acetamido-2-deoxy-d-glucopyranose)&&&&monomeric bT/bsubα/sub and bTn/b&bI/b&&GalNAc&&&bII/b, bL/b (Galβ1-4Glc, where Glc represents d-glucopyranose) and Gal (inactive). These specific binding features of ABA establish the importance of affinity enhancement by high-density polyvalent (versus multiantennary bI/b/bII/b) glycotopes and facilitate our understanding of the lectin receptor recognition events relevant to its biological activities./p