Alpha-Gal oligosaccharides: chemistry and potential biomedical application.

This article focuses on the most recent research efforts by the Wang group in the field of alpha-Gal oligosaccharides. alpha-Gal oligosaccharides are carbohydrate structures bearing a Gal alpha 1-3Gal beta terminus. This class of compounds are believed to act as xenoactive antigens that instigate the hyperacute rejection in xenotransplantation. Enzymatic methods using recombinant alpha 1-3 galactosyltransferase were employed to synthesize several alpha- Gal oligosaccharides. In addition, a chemical synthetic scheme was devised in order to produce readily acessible amounts of alpha-Gal. Conformational analysis was done using both NMR techniques and molecular modeling protocols. These studies provide important information in the structure-function relationship of alpha-Gal and anti-alpha-Gal antibodies. The second part of this article deals with the use of alpha-Gal in immunotherapy. Based on the abundance of anti-alpha-Gal antibodies IgM and IgG in human blood serum, alpha-Gal conjugates may act as effective immunotheraputic drugs. Recent studies have discovered characteristic peptide sequences containing Arg-Gly-Asp (RGD) motif that binds to integrins on the surface of cancer cells. A alpha-Gal conjugate was developed by chemical coupling a alpha-Gal trisaccharide to a RGD peptide. Preliminary studies using the conjugate on prostate DU-145 cancer cells showed a reduction in the survival rate of the cells.