title: Enzyme-assisted synthesis of a bivalent high-affinity dodecasaccharide inhibitor of mouse gamete adhesion. The length of the chains carrying distal alpha 1,3-bonded galactose residues is critical.
abstract: Proposing to study the molecular mechanisms of mouse gamete adhesion with the aid of high affinity adhesion inhibitors of saccharide nature, we report here the enzymatic synthesis of a bivalent oligosaccharide Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3(Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc (4), consisting of two long arms that link together two distal alpha 1,3-galactose residues. Binding data reported elsewhere (E. Litscher et al., Biochemistry, 1995, 34, 4662-4669) show that 4 is a high affinity inhibitor of mouse gamete adhesion in vitro (IC50 = 9 microM), while a related octasaccharide Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3(Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc, consisting of two short arms is of very low inhibitory activity. The data highlight the importance of the two alpha-galactose residues of 4, and the length of the sugar chains joining them.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Niemelä
authors.forename: L
authors.initials: L
authors.lastname: Penttilä
authors.forename: A
authors.initials: A
authors.lastname: Seppo
authors.forename: J
authors.initials: J
authors.lastname: Helin
authors.forename: A
authors.initials: A
authors.lastname: Leppänen
authors.forename: J
authors.initials: J
authors.lastname: Räbinä
authors.forename: L
authors.initials: L
authors.lastname: Uusitalo
authors.forename: H
authors.initials: H
authors.lastname: Maaheimo
authors.forename: J
authors.initials: J
authors.lastname: Taskinen
authors.forename: C E
authors.initials: CE
authors.lastname: Costello
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000187:drug effects; D004798:Enzymes; D005260:Female; D005690:Galactose / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology; D013094:Spermatozoa / Q000502:physiology
chemical_list: D004798:Enzymes; D009844:Oligosaccharides; D005690:Galactose