title: Synthesis of the glycosaminoglycan-protein linkage tetraosyl peptide moieties of betaglycan, which serve as a hexosamine acceptor for enzymatic glycosyl transfer.
abstract: Betaglycan, also known as TGF-β type III receptor, is a membrane-anchored proteoglycan, which has two glycosaminoglycan (GAG) attachment sites (López-Casillas, F.; Payne, H. M.; Andres, J. L.; Massagué, J. J.Cell Biol.1994, 124, 557-568). Chondroitin sulfate (CS) or heparan sulfate (HS) can attach to the first site, Ser(535), whereas only CS attaches to the second, Ser(546). Although the mechanism behind the assembly of CS and HS is not fully understood, it has been reported that the assembly of HS requires not only a cluster of acidic residues but also hydrophobic residues located near the Ser-Gly attachment sites (Esko, J. D. Zhang, L. Curr. Opin. Struct. Biol.1996, 6, 663-670). To further understand the effects of amino acids close to the Ser residues of the GAG-attachment sites on the glycosyltransferases, two tetraosyl peptides derived from the CS attachment sites of betaglycan, GlcA-Gal-Gal-Xyl-SerGlyAspAsnGly (1) and GlcA-Gal-Gal-Xyl-SerGlyAspAsnGlyPheProGly (2), were synthesized, and used as donor substrates for β1,4-N-acetylgalactosaminyltransferase-I (β4GalNAcT-I) and α1,4-N-acetylglucosaminyltransferase-I (α4GlcNAcT-I). Both the chemically synthesized linkage region tetrasaccharides were far better acceptors for β4GalNAcT-I than for α4GlcNAcT-I in vitro, although they also showed appreciable acceptor activity for α4GlcNAcT-I.
authors.affiliation: Department of Regional Environment, Faculty of Regional Sciences, Tottori University, Tottori 680-8551, Japan. jtamura@rstu.jp
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Tamura
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nakamura-Yamamoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Shuji
authors.initials: S
authors.lastname: Mizumoto
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D002240:Carbohydrate Sequence; D002809:Chondroitin Sulfates / Q000737:chemistry; D006025:Glycosaminoglycans / Q000138:chemical synthesis* / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry; D006595:Hexosamines / Q000737:chemistry*; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D011509:Proteoglycans / Q000138:chemical synthesis* / Q000737:chemistry; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry
chemical_list: D002809:Chondroitin Sulfates; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D006595:Hexosamines; D017350:N-Acetylgalactosaminyltransferases; D017351:N-Acetylglucosaminyltransferases; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan