Spacer-separated sialyl LewisX cyclopeptide conjugates as potential E-selectin ligands.
Completely protected sialyl LewisX azide was synthesized from a neolactosamine azide precursor carrying a 3-O-allyloxycarbonyl group as the temporary protecting group. After its Pd(0)-catalyzed deprotection and stereoselective alpha-fucosylation, the obtained LewisX azide was subjected to O-deacetylation in the galactose unit and subsequent regio- and stereoselective sialylation. Reduction of the anomeric azido group afforded the sialyl LewisX amine building block. Two molecules of this tetrasaccharide ligand were conjugated to a preformed cyclooctapeptide containing two equidistant l-asparagine units equipped with carboxy-terminated tetraethyleneglycol side chains to give, after deprotection, the target glycopeptide conjugate. Preliminary biological evaluation of the synthesized bivalent sialyl LewisX cyclopeptide conjugate showed only slightly enhanced inhibition of E-selectin binding in spite of the given flexibility of the two linked saccharide determinants.
Herzner
Holger
H
Institut für Organische Chemie, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany.
Kunz
Horst
H
D000818:Animals; D001386:Azides / Q000737:chemistry; D019040:E-Selectin / Q000737:chemistry* / Q000378:metabolism; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry; D007983:Lewis Blood Group Antigens / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
D001386:Azides; D019040:E-Selectin; D006020:Glycopeptides; D007983:Lewis Blood Group Antigens; D008024:Ligands; D009844:Oligosaccharides; D010456:Peptides, Cyclic; D000080506:Sialyl Lewis X Antigen