Modulation of cellular adhesion by glycoengineering

J Med Chem. 2010 May 27;53(10):4277-84. doi: 10.1021/jm100374g.


Aberrant glycosylation of lipid and protein molecules on cellular surfaces is responsible for many of the pathophysiological events in tumor progression and metastasis. Sialic acids in particular, are overexpressed on the glycocalyx of malignant tumor cells and sialic acid-mediated cell adhesion is required for metastasis. We report here that replacement of sialic acids on cell surfaces with fluorinated congeners dramatically decreases cell adhesion to E- and P-selectin-coated surfaces. Comparison of adhesion of fluorinated cells with those modified with nonfluorinated analogues suggests that both reduce binding of the modified sialosides to their cognate lectins to a similar extent on a per molecule basis. The overall reduction in cell adhesion results from greater cell surface presentation of the fluorinated congeners. This work suggests an avenue for inhibition of metastasis by administration of small molecules and concomitant noninvasive imaging of tumor cells by (19)F MRI before they are visible by other means.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Adhesion / drug effects
  • E-Selectin / chemistry
  • Extracellular Matrix Proteins / chemistry
  • Fluorine
  • Glycocalyx / chemistry*
  • HL-60 Cells
  • Humans
  • Models, Molecular
  • P-Selectin / chemistry
  • Sialic Acids / chemical synthesis*
  • Sialic Acids / chemistry
  • Sialic Acids / pharmacology
  • Structure-Activity Relationship


  • E-Selectin
  • Extracellular Matrix Proteins
  • P-Selectin
  • Sialic Acids
  • Fluorine