Biochemical engineering of the acyl side chain of sialic acids stimulates integrin-dependent adhesion of HL60 cells to fibronectin.
Sialylation of glycoproteins and glycolipids plays an important role during development, regeneration and pathogenesis of several diseases. The physiological precursor of all sialic acids is N-acetyl- D-mannosamine. The N-acyl side chain of sialic acid can be modified by exposure of cells to synthetic N-acyl-modified D-mannosamines. In a new experimental approach cells were cultivated in the presence of N-propanoyl- D-mannosamine. This unnatural precursor of sialic acid is taken up by cells and efficiently metabolized to the respective N-acyl-modified neuraminic acid in vitro and in vivo. Here we report on the biological consequences of the incorporation of the unnatural N-propanoylneuraminic acid into glycoconjugates of HL60 cells. Biochemical engineering of the acyl side chain of neuraminic acids activates beta(1)-integrins (VLA4 or VLA5), resulting in an increased adhesion of HL60 cells to fibronectin.
Villavicencio-Lorini
Pablo
P
Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Arnimallee 22, 14195 Berlin-Dahlem, Germany.
Laabs
Stephan
S
Danker
Kerstin
K
Reutter
Werner
W
Horstkorte
Rüdiger
R
D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D018929:Cell Culture Techniques; D005353:Fibronectins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000494:pharmacology; D012794:Sialic Acids / Q000494:pharmacology*
D005353:Fibronectins; D006023:Glycoproteins; D019012:Integrin beta1; D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid