Agonists and antagonists of carbohydrate-protein interactions are useful as biological probes and therapeutic agents. Designing multivalent probes, however, requires detailed information about the complex structure, density, spacing and orientation of carbohydrate ligands as well as the multiple binding sites of lectins, many of which have unknown space and geometries.  A new method of obtaining a multivalent inhibitor without structural information about the lectin and receptor could accelerate discovery of new therapies.  Here, we develop a new format array via spacing neoglycoproteins apart with unconjugated BSA to identify multivalent inhibitors. The array is composed of 591 combinations of glycan structure and presentation. First, we test three plant lectins with well known specificity and structure, ConA, VVL-B4, and RCA. Finally, the doping array was used to identify potent multivalent inhibitors of Pseudomonas aeruginosa lectin I (PA-IL), a bacterial lectin, and mouse macrophage galactose-type lectin (mMGL-2), a potential vaccine targeting receptor.

New format carbohydrate microarray: Its application for identification of multivalent inhibitors

240th National Meeting (2010)

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