The objective of our research program is to probe key questions in biological chemistry using the tools of the organic chemist. Currently, we seek to understand the protein-carbohydrate interactions that are involved in cell signaling; ultimately, we plan to use this information to formulate multivalent therapeutic agents and vaccines. In this proposal, we describe a novel dendrimer-based system from which artificial multivalent carbohydrate-containing systems will be developed. The techniques we're developing make our system uniquely suited for probing the underlying causes of the multivalent effect in protein- carbohydrate interactions. In addition, the new methods we describe for rapid synthesis of heterogeneously-functionalized dendrimer surfaces are widely applicable. A new method for incorporation of varying concentrations of mannose units onto the surface of G(4)- and G(6)-PAMAM dendrimers is outlined. Evaluation of the interaction of carbohydrate-functionalized dendrimers with lectins using microcalorimetry, hemagglutination, an enzyme-linked lectin assay, and an affinity column/EPR study is proposed. A strategy for EPR characterization of the new dendrimer motifs using TEMPO-labeled dendrimers is also presented.
| Cousin, Jonathan M; Cloninger, Mary J (2016) The Role of Galectin-1 in Cancer Progression, and Synthetic Multivalent Systems for the Study of Galectin-1. Int J Mol Sci 17: |
| VanKoten, Harrison W; Dlakic, Wendy M; Engel, Robert et al. (2016) Synthesis and Biological Activity of Highly Cationic Dendrimer Antibiotics. Mol Pharm 13:3827-3834 |
| Wolfenden, Mark; Cousin, Jonathan; Nangia-Makker, Pratima et al. (2015) Glycodendrimers and Modified ELISAs: Tools to Elucidate Multivalent Interactions of Galectins 1 and 3. Molecules 20:7059-96 |
| Cousin, Jonathan M; Cloninger, Mary J (2015) Glycodendrimers: tools to explore multivalent galectin-1 interactions. Beilstein J Org Chem 11:739-47 |
| Michel, Anna K; Nangia-Makker, Pratima; Raz, Avraham et al. (2014) Lactose-functionalized dendrimers arbitrate the interaction of galectin-3/MUC1 mediated cancer cellular aggregation. Chembiochem 15:2106-12 |
| Goodman, Candace K; Wolfenden, Mark L; Nangia-Makker, Pratima et al. (2014) Multivalent scaffolds induce galectin-3 aggregation into nanoparticles. Beilstein J Org Chem 10:1570-7 |
| Mattson, Amanda L; Michel, Anna K; Cloninger, Mary J (2012) Using In(III) as a promoter for glycosylation. Carbohydr Res 347:142-6 |
| Sebby, Karl B; Walter, Eric D; Usselman, Robert J et al. (2011) End-group distributions of multiple generations of spin-labeled PAMAM dendrimers. J Phys Chem B 115:4613-20 |
| Schlick, Kristian H; Morgan, Joel R; Weiel, Julianna J et al. (2011) Clusters of ligands on dendrimer surfaces. Bioorg Med Chem Lett 21:5078-83 |
| Schlick, Kristian H; Cloninger, Mary J (2010) Inhibition binding studies of glycodendrimer-lectin interactions using surface plasmon resonance. Tetrahedron 66:5305-5310 |
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