Targeting CD22 with Sialic Acid Derivatives

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1st EuroCarb Young Researcher (ECYR) Workshop

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Mini symposium: Glycobiology at the LUMC and beyond

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Targeting CD22 with Sialic Acid Derivatives

June Ereño Orbea , Lijuan Pang, Hong Cui, Dorota Borovsky, Corwin Nycholat, Christoph Rademacher, Jim Paulson, Jean-Philippe Julien

1 Cicbiogune, Derio, Spain

CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that maintains a baseline level of B cell inhibition. Its function and restricted expression in B cells makes CD22 a validated target in therapies against deregulated B cells that cause B cell lymphomas and autoimmune diseases. High-affinity sialic acid based ligands that will compete with natural sialic acid ligands to bind CD22 represent a promising therapeutic tool. Here, we describe the design and synthesis of a sialoside library constructed by chemical modifications on carbon substituents C2, C5 and C9 on the natural Neu5Ac scaffold. We have solved the crystal structures of the most N-terminal three Ig domains (d1-d3) of human CD22 in complex with three different sialic acid derivatives. Our results provide a strategy to generate high affinity sialic acid molecules against CD22 that will outcompete the natural ligand for the receptor and modulate its activity.

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