Engineering the sialic acid in organs of mice using N-propanoylmannosamine

• Published in: Biochimica et biophysica acta Vol. 1770; no. 2; pp. 297 - 306
• Main Authors: Gagiannis, Daniel, Gossrau, Reinhart, Reutter, Werner, Zimmermann-Kordmann, Martin, Horstkorte, Rüdiger
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2007
• Subjects: Animals; Biochemical engineering; Brain - metabolism; Cell Membrane - metabolism; Flow Cytometry; Genetic Engineering; Hexosamines - metabolism; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal - metabolism; Myocardium - metabolism; N-Acetylneuraminic Acid - biosynthesis; N-Acetylneuraminic Acid - blood; N-Acetylneuraminic Acid - metabolism; Neural cell adhesion molecule; Organ Specificity; Polysialic acid; Sialic acid; Subcellular Fractions - metabolism; Sialic acid; Neural cell adhesion molecule; Biochemical engineering; Polysialic acid
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2006.09.023

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.