Engineering the sialic acid in organs of mice using N-propanoylmannosamine.
Sialic acids play an important role during development, regeneration and pathogenesis. The precursor of most physiological sialic acids, such as N-acetylneuraminic acid is N-acetyl-D-mannosamine. Application of the novel N-propanoylmannosamine leads to the incorporation of the new sialic acid N-propanoylneuraminic acid into cell surface glycoconjugates. Here we analyzed the modified sialylation of several organs with N-propanoylneuraminic acid in mice. By using peracetylated N-propanoylmannosamine, we were able to replace in vivo between 1% (brain) and 68% (heart) of physiological sialic acids by N-propanoylneuraminic acid. The possibility to modify cell surfaces with engineered sialic acids in vivo offers the opportunity to target therapeutic agents to sites of high sialic acid concentration in a variety of tumors. Furthermore, we demonstrated that application of N-propanoylmannosamine leads to a decrease in the polysialylation of the neural cell adhesion molecule in vivo, which is a marker of poor prognosis for some tumors with high metastatic potential.
Gagiannis
Daniel
D
Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195 Berlin-Dahlem, Germany.
Gossrau
Reinhart
R
Reutter
Werner
W
Zimmermann-Kordmann
Martin
M
Horstkorte
Rüdiger
R
D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005434:Flow Cytometry; D005818:Genetic Engineering; D006595:Hexosamines / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D009928:Organ Specificity; D013347:Subcellular Fractions / Q000378:metabolism
D006595:Hexosamines; C076271:N-propanoylmannosamine; D019158:N-Acetylneuraminic Acid; C002022:N-acetylmannosamine