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A series of enzymatic substitutions modifies the basic structure of complex-type biantennary N-glycans. Among them, a b1,2-linked N-ace-tylglucosamine residue is introduced to the central mannose moiety of the core-fucosylated oligosaccharide by N-acetylglucosaminyltransferase VII. This so-called LEC14 epitope can undergo galactosylation at theb1,2-linked N-acetylglucosamine residue. | iFEBS Journal Introduction of extended LEC14-type branching into core-fucosylated biantennary N-glycan Glycoengineering for enhanced cell binding and serum clearance of the neoglycoprotein Sabine Andre1 Shuji Kojima2 Ingo Prahl3 Martin Lensch1 Carlo Unverzagt3 and Hans-Joachim Gabius1 1 Institut fur Physiologische Chemie Tierarztliche Fakultejt Ludwig-Maximilians-Universitat Munchen Germany 2 Faculty of PharmaceuticalSciences Tokyo University of Science Japan 3 Bioorganische Chemie Universitat Bayreuth Germany Keywords drug targeting galectin glycosylation lectin tumor imaging Correspondence S. Andre Institut fur Physiologische Chemie Tierarztliche Fakultat Ludwig-Maximilians-Universitat Munchen Veterinarstr. 13 80539 Munchen Germany Fax 49 80 2180 2508 Tel 49 89 2180 2290 E-mail Sabine.Andre@lmu.de Received 16 December 2004 revised 23 February 2005 accepted 2 March 2005 doi 10.1111 j.1742-4658.2005.04637.x A series of enzymatic substitutions modifies the basic structure of complex-type biantennary N-glycans. Among them a pi 2-linked N-ace-tylglucosamine residue is introduced to the central mannose moiety of the core-fucosylated oligosaccharide by N-acetylglucosaminyltransferase VII. This so-called LEC14 epitope can undergo galactosylation at the p1 2-linked N-acetylglucosamine residue. Guided by the hypothesis that structural modifications in the N-glycan alter its capacity to serve as ligand for lectins we prepared a neoglycoprotein with the extended LEC14 N-glycan and tested its properties in three different assays. In order to allow comparison to previous results on other types of biantennary N-glycans the functionalization of the glycans for coupling and assay conditions were deliberately kept constant. Compared to the core-fucosylated N-glycan no significant change in affinity was seen when testing three galactoside-specific proteins. However cell positivity in flow cytofluorimetry was enhanced in six of eight human tumor lines. Analysis of biodistribution in
