Biochemical engineering of the side chain of sialic acids increases the biological stability of the highly sialylated cell adhesion molecule CEACAM1.
The biological half-life time of many glycoproteins is regulated via terminal sialic acids. In this study we determined the half-lives of two different cell adhesion molecules, CEACAM1 and the alpha1-integrin subunit, in PC12-cells before and after biochemical engineering the side chain of sialic acids by the use of N-propanoylmannosamine. Both are transmembrane glycoproteins. While the immunoglobulin superfamily member CEACAM1 mediates homophilic cell-cell adhesion the alpha1-integrin subunit is involved in cell-matrix interactions. We found that the half-life of the highly sialylated CEACAM1 is increased from 26 to 40 h by replacement of the N-acetylneuraminic acid by the novel, engineered N-propanoylneuraminic acids, whereas the half-life of the alpha1-integrin subunit remains unaffected under the same conditions. This demonstrates that biochemical engineering not only modulates the structure of cell surface sialic acids, but that biochemical engineering also influences biological stability of defined glycoproteins.
Horstkorte
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Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Arnimallee 22, Berlin-Dahlem, D-14195, Germany. rhorstke@zedat.fu-berlin.de
Lee
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Lucka
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Danker
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Mantey
L
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Reutter
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W
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000737:chemistry* / Q000378:metabolism*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D006595:Hexosamines / Q000378:metabolism; D039423:Integrin alpha1; D009438:Neuraminic Acids / Q000032:analysis / Q000378:metabolism; D016716:PC12 Cells / Q000378:metabolism; D015202:Protein Engineering; D051381:Rats; D012794:Sialic Acids / Q000737:chemistry*
D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D006595:Hexosamines; D039423:Integrin alpha1; C425503:N-propanoylneuraminic acid; D009438:Neuraminic Acids; D012794:Sialic Acids; C076271:N-propanoylmannosamine