α-Gal oligosaccharides: Chemistry and potential biomedical application

This article focuses on the most recent research efforts by the Wang group in the field of α-Gal oligosaccharides, α-Gal oligosaccharides are carbohydrate structures bearing a Galα1-3Galβ terminus. This class of compounds are believed to act as xenoactive antigens that instigate the hyperacute rejection in xenotransplantation. Enzymatic methods using recombinant α1-3 galactosyltransferase were employed to synthesize several α-Gal oligosaccharides. In addition, a chemical synthetic scheme was devised in order to produce readily acessible amounts of α-Gal. Conformational analysis was done using both NMR techniques and molecular modeling protocols. These studies provide important information in the structure-function relationship of α-Gal and anti-α-Gal antibodies. The second part of this article deals with the use of α-Gal in immunotherapy. Based on the abundance of anti-α-Gal antibodies IgM and IgG in human blood serum, α-Gal conjugates may act as effective immunotherapeutic 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 α-Gal conjugate was developed by chemical coupling a α-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.