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Engineering the sialic acid in organs of mice using N-propanoylmannosamine
Authors:Daniel Gagiannis,Reinhart Gossrau,Werner Reutter,Martin Zimmermann-Kordmann,Rü  diger Horstkorte
Affiliation:1. Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195 Berlin-Dahlem, Germany;2. Institut für Integrative Neuroanatomie, Charité-Universitätsmedizin Berlin, Campus Mitte, Philippstr. 12’ 10117 Berlin, Germany
Abstract: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.
Keywords:Sialic acid   Polysialic acid   Neural cell adhesion molecule   Biochemical engineering
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