http://precedings.nature.com/users/45b30ba952925159a47d0c6e62829c11/ Documents posted by James Paulson Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://dx.doi.org/10.1038/npre.2009.3549.1 Multivalent ligands of CD22 for active targeting of B cells. Mary O’Reilly, Wei Hsu Chen, Gladys Completo, Ying Zeng, Satoshi Futakawa and Cory Rillahan and James C. Paulson, Departments of Chemical Physiology and Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037The siglecs comprise 13 members of the immunoglobulin superfamily that recognize sialic acid containing glycans, and are differentially expressed on leukocytes and glial cells. The natural ligands of siglecs typically occur on the same cell (in cis) and/or on adjacent cells (in trans). Cis ligands mask the binding of multivalent synthetic sialoside ligands and are thought to regulate the activity of siglecs as modulators of cell signaling. However, synthetic ligands of sufficient avidity can compete with cis ligands, demonstrating a dynamic equilibrium of cis and trans ligand probes. We have explored the relationship between valency, affinity and geometry for achieving avidity sufficient to compete with cis ligands of CD22 (Siglec-2) in situ. A notable achievement is a hetero-bifunctional ligand approach to create multivalent ligands using antibodies as a protein scaffold. The ligand is comprised of a CD22 ligand, 9-biphenylcarboxyl-NeuAcα2-6Galβ1-4GlcNAc (BPCNeuAc), coupled to an antigen, 4-hydroxy-3-nitrophenylacetic acid (NP) (BPCNeuAc-NP). The BPCNeuAc-NP ligand is able to efficiently assemble complexes of anti-NP antibodies with CD22 on both asialo- and native B cells. Surprisingly, assembly of the tertiary complex occurs with anti-NP IgM (n=10), IgA (n=4) and IgG (n=2). The results suggest that spacing of ligands using an antibody optimizes the contribution of geometry to achieve high avidity with low valency. Other multivalent configurations also show promise for targeting B cells. In particular, liposomes bearing BPCNeuAc ligands bind avidly to B cells and are endocytosed. Thus, BPCNeuAc-lipososomes may prove effective in delivery of therapeutic agents to B cells (Supported by NIH grants GM60938, AI50143 ). http://dx.doi.org/10.1038/npre.2009.3549.1 Wed, 05 Aug 2009 08:41:59 UTC Multivalent ligands of CD22 for targeting of B cells doi:10.1038/npre.2009.3549.1 2009-08-05 James C. Paulson Nature Precedings 2009-08-05T08:41:59Z Presentation Biotechnology Cancer Chemistry Immunology Molecular Cell Biology http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2007.15.1 Presentation in the Human Glycomics Proteomics Disease Initiative (HGPI) session. http://dx.doi.org/10.1038/npre.2007.15.1 Thu, 18 Jan 2007 05:24:57 UTC Bioinformatics Approach for Functional Glycomics doi:10.1038/npre.2007.15.1 2007-01-18 James C. Paulson Nature Precedings 2007-01-18T05:24:57Z Presentation Molecular Cell Biology Bioinformatics http://creativecommons.org/licenses/by/2.5/ http://dx.doi.org/10.1038/npre.2007.12.1 This presentation summarizes developments in glycan and pathogen polysaccharide arrays at the Consortium for Functional Glycomics (CFG). http://dx.doi.org/10.1038/npre.2007.12.1 Tue, 16 Jan 2007 04:56:05 UTC Developments in CFG glycan and pathogen polysaccharide arrays doi:10.1038/npre.2007.12.1 2007-01-16 Ola Blixt Nature Precedings 2007-01-16T04:56:05Z Presentation Chemistry Molecular Cell Biology Bioinformatics http://creativecommons.org/licenses/by/2.5/ http://dx.doi.org/10.1038/npre.2007.11.1 This presentation provides an overview of the Consortium for Functional Glycomics. http://dx.doi.org/10.1038/npre.2007.11.1 Tue, 16 Jan 2007 04:50:15 UTC Consortium for Functional Glycomics Overview doi:10.1038/npre.2007.11.1 2007-01-16 James C. Paulson Nature Precedings 2007-01-16T04:50:15Z Presentation Chemistry Molecular Cell Biology Bioinformatics http://creativecommons.org/licenses/by/2.5/