Targeting Human CD22/Siglec-2 with Dimeric Sialosides as Novel Oligosaccharide Mimetics
Prescher H, Schweizer A, Frank M, Kuhfeldt E, Ring J, Nitschke L (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 65
Pages Range: 10588-10610
Journal Issue: 15
DOI: 10.1021/acs.jmedchem.2c00765
Abstract
Significant interest in the development of high-affinity ligands for Siglecs exists due to the various therapeutically relevant functions of these proteins. Here, we report a new strategy to develop and design Siglec ligands as disialyl-oligosaccharide mimetics exemplified on Siglec-2 (CD22). We report insights into development of dimeric ligands with high affinity and avidity to cell surface-expressed CD22, assay development, tool compounds, structure activity relationships, and biological data on calcium flux regulation in B-cells. The binding modes of selected ligands have been modeled based on state-of-the-art molecular dynamics simulations on the microsecond timescale, providing detailed views on ligand binding and opening a new perspective on drug design efforts for Siglecs. High-avidity dimeric ligands containing a linker opening the way towards bispecifics are presented as well.
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Germany (DE)
Sweden (SE)How to cite
APA:
Prescher, H., Schweizer, A., Frank, M., Kuhfeldt, E., Ring, J., & Nitschke, L. (2022). Targeting Human CD22/Siglec-2 with Dimeric Sialosides as Novel Oligosaccharide Mimetics. Journal of Medicinal Chemistry, 65(15), 10588-10610. https://doi.org/10.1021/acs.jmedchem.2c00765
MLA:
Prescher, Horst, et al. "Targeting Human CD22/Siglec-2 with Dimeric Sialosides as Novel Oligosaccharide Mimetics." Journal of Medicinal Chemistry 65.15 (2022): 10588-10610.
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