Effect of polyvalencies of glycotopes on the binding of a lectin from the edible mushroom, Agaricus bisporus.
Agaricus bisporus 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 Galbeta1-3GalNAc (T; 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 Galbeta1-related glycotopes, GalNAcalpha1-Ser/Thr (Tn), and their cryptoforms, are the most potent factor for ABA binding. They were up to 5.5x10(5) and 4.7x10(6) times more active than monomeric T and GalNAc respectively. The affinity of ABA for ligands can be ranked as: multivalent T (alpha) (Galbeta1-3GalNAcalpha1-), Tn and I / II (Galbeta1-3GlcNac/Galbeta1-4GlcNAc, where GlcNAc represents 2-acetamido-2-deoxy-D-glucopyranose)>>>>monomeric T (alpha) and Tn > I >>GalNAc>>> II, L (Galbeta1-4Glc, 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 I / II) glycotopes and facilitate our understanding of the lectin receptor recognition events relevant to its biological activities.
Wu
Albert M
AM
Glyco-Immunochemistry Research Laboratory, Institute of Molecular and Cellular Biology, Chang-Gung University, Kwei-San, Tao-Yuan 333, Taiwan. amwu@mail.cgu.edu.tw
Wu
June H
JH
Herp
Anthony
A
Liu
Jia-Hau
JH
D000363:Agaricales / Q000737:chemistry; D000364:Agaricus / Q000737:chemistry*; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D037102:Lectins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry* / Q000302:isolation & purification; D000509:alpha-Fetoproteins / Q000737:chemistry
C041433:Agaricus lectins; D006023:Glycoproteins; D037102:Lectins; D009844:Oligosaccharides; D011134:Polysaccharides; D000509:alpha-Fetoproteins