A solid phase carbohydrate library was synthesized and screened against Bauhinia purpurea lectin. The library, which contains approximately 1300 di- and trisaccharides, was synthesized with chemical encoding on TentaGel resin so that each bead contained a single carbohydrate. Two ligands that bind more tightly to the lectin than Gal-beta-1,3-GalNAc (the known ligand) have been identified. The strategy outlined can be used to identify carbohydrate-based ligands for any receptor; however, because the derivatized beads mimic the polyvalent presentation of cell surface carbohydrates, the screen may prove especially valuable for discovering new compounds that bind to proteins participating in cell adhesion.

Numerous studies have established that polyvalency is a critical feature of cell surface carbohydrate recognition. Nevertheless, carbohydrate-protein interactions are typically evaluated by using assays that focus on the behavior of monovalent carbohydrate ligands in solution. It has generally been assumed that the relative affinities of monovalent carbohydrate ligands in solution correlate with their polyvalent avidities. In this paper we show that carbohydrate ligands synthesized directly on TentaGel beads interact with carbohydrate-binding proteins in a polyvalent manner. The carbohydrate-derivatized beads can, therefore, be used as model systems for cell surfaces to evaluate polyvalent carbohydrate-protein interactions. By using a combinatorial approach to synthesize solid-phase libraries of polyvalent carbohydrates, one can rapidly address key issues in the area of cell surface carbohydrate recognition. For example, studies reported herein demonstrate that there is an unanticipated degree of specificity in recognition processes involving polyvalent carbohydrates. However, the correlation between polyvalent avidities and solution affinities is poor. Apparently, the presentation of carbohydrates on the polymer surface has a profound inf luence on the interaction of the ligand with the protein receptor. These findings have implications for how carbohydrates function as recognition signals in nature, as well as for how polyvalent carbohydrate-protein interactions should be studied.Interactions between carbohydrates on the surface of one cell type and proteins on the surface of another cell type play critical roles in a wide variety of biochemical recognition processes (1, 2). However, the details of these interactions are poorly understood. Typically, receptor-ligand binding events are studied by making derivatives of the ligand and directly quantitating the affinity. Applying this approach to cell surface carbohydrates has been problematic because carbohydrates are notoriously difficult to synthesize; it is usually not feasible to make more than a small number of derivatives, and even that can take years (3). Moreover, it is difficult to measure the binding affinities by using direct methods because individual carbohydrates bind weakly (K d Ϸ 10 Ϫ3 M) to their protein receptors. Therefore, the relative affinities of carbohydrates are obtained from the concentrations of ligand required to inhibit some event or process-e.g., cell agglutination-that is caused by interactions between the protein receptor and carbohydrates presented on the cell surface. These inhibition assays have shown that many carbohydrate-binding proteins can bind a variety of different structures with similar affinities (4). The broad specificity makes it hard to evaluate which structural features are critical for recognition.Despite the low affinity and broad specificity of individual carbohydrate-protein interactions, carbohydrates function as very specific signals in a wide variety of cell-cell recognition events. Proteins involved...