We are using dendrimers (macromolecules consisting of a series of branches around an inner core) to study the interaction of carbohydrates with receptor proteins called lectins. Although a wide variety of biological processes including fertilization, development, and the mounting of an immune response rely on protein-carbohydrate interactions for cellular recognition and adhesion (Figure 1), these interactions are not well understood. Because the affinity of lectins for individual saccharide units is relatively weak, the adhesion of lectins to saccharides on the surface of a cell involves multipoint attachment (multivalency).

We are using saccharide-functionalized poly(amidoamine) (PAMAM) dendrimers (Figure 2) to learn more about multivalency in protein carbohydrate interactions. Dendrimers are ideal frameworks for the study of how systematic structural changes alter the way that a glycopolymer interacts with a protein. In addition to changing the dendrimer generation, the degree of carbohydrate loading on a dendrimer can also be readily changed by controlling the number of equivalents of sugar residues that are added to the dendrimer (Figure 3). We can systematically and predictably attenuate the relative affinities of the dendrimers for the lectins by incorporating low and high affinity ligands into the dendrimer. We can also influence how many proteins bind to each dendrimer. We're evaluating the comparative activity of these dendrimers for lectins such as Concanavalin A, Pisum Sativum, and Cyanovirin N using a variety of assays. In this way, we are learning about the factors that control physiologically relevant multivalent protein-carbohydrate interactions. Because of their ready tunability, the carbohydrate functionalized dendrimers described here should provide guidelines for the development of synthetic multivalent frameworks for many applications in chemical biology.

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Biochemistry, Chemical Biology, Organic