title: Selective inhibition of polysialyltransferase ST8SiaII by unnatural sialic acids.
abstract: Polysialic acid (polySia) is a unique and highly regulated posttranslational modification of the neural cell adhesion molecule (NCAM). The presence of polySia affects NCAM-dependent cell adhesion and plays an important role during brain development, neural regeneration and plastic processes including learning and memory. Polysialylated NCAM is expressed on several neuroendocrine tumors of high malignancy and correlates with poor prognosis. Two closely related enzymes, the polysialyltransferases ST8SiaII and ST8SiaIV, catalyze the biosynthesis of polySia. However, the impact of each enzyme in NCAM polysialylation is not understood. Here, we describe the selective cell-based in vitro inhibition of ST8SiaII using synthetic sialic acid precursors. We provide evidence for different substrate affinities of ST8SiaII and ST8SiaIV. These data open the possibility to study the individual role of the two enzymes during various aspects of brain development and function and in tumorigenesis.
authors.affiliation: Institut für Molekularbiologie und Biochemie, Charité-Universitätsmedizin Berlin, D-14195 Berlin-Dahlem, Germany. ruediger.horstkorte@charite.de
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Horstkorte
authors.forename: Martina
authors.initials: M
authors.lastname: Mühlenhoff
authors.forename: Werner
authors.initials: W
authors.lastname: Reutter
authors.forename: Sabine
authors.initials: S
authors.lastname: Nöhring
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann-Kordmann
authors.forename: Rita
authors.initials: R
authors.lastname: Gerardy-Schahn
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D020134:Catalytic Domain / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D018922:HL-60 Cells; D006595:Hexosamines / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009438:Neuraminic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012799:Sialyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D006595:Hexosamines; D019006:Neural Cell Adhesion Molecules; D009438:Neuraminic Acids; C008322:mannosamine; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid