Abstract
Potential E- and P-selectin inhibitors were synthesized to explore a hydrophobic area on the E-selectin surface and the PSGL-1 protein binding site on the P-selectin surface that was recently defined by crystallography. Three series of mannose-based compounds (libraries A, B, and C) were synthesized using solution phase parallel synthesis. Biological evaluation of these compounds was done using two ELISA-based assays and transferred NOE (trNOE) experiments. Some of the compounds showed better activity than sLe(x) in the P-selectin assay.
MeSH terms
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Combinatorial Chemistry Techniques
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Crystallography, X-Ray
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E-Selectin / chemistry*
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Enzyme-Linked Immunosorbent Assay
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Humans
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Ligands
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Magnetic Resonance Spectroscopy
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Mannosides / chemical synthesis*
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Mannosides / chemistry
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Membrane Glycoproteins / chemistry
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Models, Molecular
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Oligosaccharides / chemistry
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P-Selectin / chemistry*
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Protein Binding
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Sialyl Lewis X Antigen
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Structure-Activity Relationship
Substances
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E-Selectin
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Ligands
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Mannosides
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Membrane Glycoproteins
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Oligosaccharides
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P-Selectin
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P-selectin ligand protein
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Sialyl Lewis X Antigen