Cell-surface carbohydrate recognition binding

One important area of current research is on the recognition of carbohydrates. In particular, cell surface carbohydrates have implications in various disease states. In some forms of cancer, closely packed cell surface carbohydrates effect cancer progression and invasiveness. Many of these carbohydrates have terminal sialic acid groups. The pinwheel receptor 42 was designed as a divalent receptor for anionic sugars including sialic acid with a view toward making sensors for cancer markers. Sensor 42 used a boronic acid to bind a diol on the... 

The precise chemical interactions between an adhesin and its receptor are also important. For example, direct- and water-mediated hydrogen bonds are the most important interactions within the carbohydrate-recognition domain in carbohydrate-binding adhesins on the host cell surface (Weis and Drickamer, 1996). Nonpolar van der Waals interactions and hydrophobic "stacking of the receptor oligosaccharide rings with aromatic amino acid side chains of the bacterial adhesin protein also contribute to oligosaccharide-protein interactions. X-ray structural... 

Several laboratories have studied the assimilation of specific lysosomal enzymes using as model systems skin fibroblasts deficient in the enzyme under study. The underlying mechanism for the translocation of lysosomal enzymes was hypothesized to involve binding of carbohydrate-containing recognition markers to specific cell surface receptors (1 5). In support of this hypothesis Hickman, Shapiro, and Neufeld (16J found that treatment of N-acetyl-B-hexosaminidase with periodate under conditions that dTd not affect enzymatic activity prevented the efficient assimilation of this enzyme by Sandhoff fibroblasts. Additionally, Kresse and von Figura (1 7) found that treatment of f -acetyl-a-hexosaminidase with B-galactosidase reduced the assimilation of this enzyme by San-filippo B fibroblasts. 

The observation that phosphate-free glycopeptides at low concentrations effectively inhibit the assimilation of 8-galacto-sidase by fibroblasts implies that details of the carbohydrate structure play a role in enzyme recognition by cells. The role of phosphate in the assimilation of lysosomal enzymes remains obscure. Conceivably, phosphate may lend additional specificity to the assimilation system, or perhaps it could play a role in events subsequent to the initial binding of the enzyme to the cell surface. 

---