title: The Galβ-(syn)-gauche configuration is required for galectin-recognition disaccharides.
abstract: BACKGROUND
  Galectins form a large family of animal lectins, individual members having variously divergent carbohydrate-recognition domains (CRDs) responsible for extensive physiological phenomena. Sugar-binding affinities of galectins were previously investigated by us using frontal affinity chromatography (FAC) with a relatively small set (i.e., 41) of oligosaccharides. However, total understanding of a consensus rule for galectin-recognition saccharides is still hampered by the lack of fundamental knowledge about their sugar-binding specificity toward a much larger panel of oligosaccharides in terms of dissociation constant (K(d)).
  
  
  METHODS
  In the present study, we extended a FAC analysis from a more systematic viewpoint by using 142 fluorescent-labeled oligosaccharides, initially with focus on functional human galectins-1-9. Binding characteristics were further validated with 11 non-human galectins and 13 non-galectin Gal/GalNAc-binding lectins belonging to different families.
  
  
  RESULTS
  An empirical [Galβ-equatorial] rule for galectin-recognition disaccharides was first derived by our present research and previous works by others. However, this rule was not valid for a recently reported nematode disaccharide, "Galβ1-4-L-Fuc" [Butschi et al. PLoS Pathog, 2010; 6(1):e1000717], because this glycosidic linkage was directed to 'axial' 4-OH of L-Fuc. After careful reconsideration of the structural data, we reached an ultimate rule of galectin-recognition disaccharides, which all of the galectins so far identified fulfilled, i.e., under the re-defined configuration "Galβ-(syn)-gauche". The rule also worked perfectly for differentiation of galectins from other types of lectins.
  
  
  CONCLUSIONS
  The present attempt should provide a basis to solve the riddle of the glyco-code as well as to develop therapeutic inhibitors mimicking galectin ligands.
authors.affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Iwaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tateno
authors.forename: Nozomu
authors.initials: N
authors.lastname: Nishi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Minamisawa
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nakamura-Tsuruta
authors.forename: Yoko
authors.initials: Y
authors.lastname: Itakura
authors.forename: Junko
authors.initials: J
authors.lastname: Kominami
authors.forename: Tadasu
authors.initials: T
authors.lastname: Urashima
authors.forename: Takanori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Jun
authors.initials: J
authors.lastname: Hirabayashi
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D002846:Chromatography, Affinity / Q000295:instrumentation / Q000379:methods*; D004187:Disaccharides / Q000737:chemistry* / Q000378:metabolism; D037161:Galectins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D004187:Disaccharides; D037161:Galectins; D009844:Oligosaccharides; D020033:Protein Isoforms; D011994:Recombinant Proteins