Abstract
Purpose. Common oligosaccharides of cellularglycoconjugates are ligands for more than one type of endogenous lectin.Overlapping specificities to β-galactosides of C-type lectins andgalectins can reduce target selectivity of carbohydrate-ligand-dependentdrug targeting. The purpose of this study is to explore distinct features ofligand presentation and structure for design of cluster glycosides todistinguish between asialoglycoprotein-specific (C-type) lectins andgalectins.
Methods. Extent of binding of labeled sugar receptors totwo types of matrix-immobilized (neo)glycoproteins and to cells wasevaluated in the absence and presence of competitive inhibitors. This panelcomprised synthetic mono-, bi-, and trivalent glycosides with two spacerlengths and galactose or lactose as ligand part.
Results. In contrast to C-type lectins of hepatocytes andmacrophages, bi- and trivalent glycosides do not yield a notable glycosidecluster effect for galectins-1 and -3. Also, theseCa2+-independent galactoside-binding proteins prefer to homein on lactose-bearing glycosides relative to galactose as ligand, whilespacer length requirements were rather similar.
Conclusions. Trivalent cluster glycosides with Gal/GalNAcas ligand markedly distinguish between C-type lectins and galectins.Undesired side reactivities to galectins for C-type lectin drug deliverywill thus be minimal.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
M. J. Poznansky and R. L. Juliano. Biological approaches to the controlled delivery of drugs: A critical review. Pharmacol. Rev. 36:277–336 (1984).
H.-J. Gabius. Detection and functions of mammalian lectins·with emphasis on membrane lectins. Biochim. Biophys. Acta 1071:1–18 (1991).
D. K. F. Meijer and G. Molema. Targeting of drugs to the liver. Sem. Liver Dis. 15:202–256 (1995).
K. G. Rice. Glycoconjugate-mediated drug targeting. In H.-J. Gabius and S. Gabius (eds.) Glycosciences: Status and Perspectives, Chapman & Hall, London, 1997, pp. 471–483.
R. A. Laine. The information-storing potential of the sugar code. In H.-J. Gabius and S. Gabius (eds.) Glycosciences: Status and Perspectives, Chapman & Hall, London, 1997, pp. 1–14.
G. Reuter and H.-J. Gabius. Eukaryotic glycosylation: Whim of nature or multipurpose tool? Cell. Mol. Life Sci. 55:368–422 (1999).
G. Ashwell and J. Harford. Carbohydrate-specific receptors of the liver. Annu. Rev. Biochem. 51:531–554 (1982).
P. H. Weigel. Galactosyl and N-acetylgalactosaminyl homeostasis: A function for mammalian asialoglycoprotein receptors. BioEssays 16:519–524 (1994).
H.-J. Gabius. Animal lectins. Eur. J. Biochem. 243:543–576 (1997).
R. T. Lee and Y. C. Lee. Enhanced biochemical affinities of multivalent neoglycoconjugates. In Y. C. Lee and R. T. Lee (eds.) Neoglycoconjugates: Preparation and Applications, Academic Press, San Diego, 1994, pp. 23–50.
R. T. Lee and Y. C. Lee. Neoglycoconjugates. In H.-J. Gabius and S. Gabius (eds.) Glycosciences: Status and Perspectives, Chapman & Hall, London, 1997, pp. 55–77.
K. Ozaki, R. T. Lee, Y. C. Lee, and T. Kawasaki. The differences in structural specificity for recognition and binding between asialoglycoprotein receptors of liver and macrophages. Glycoconjugate J. 12:268–274 (1995).
A. Kichler and F. Schuber. Comparative affinity of synthetic multiantennary galactosyl derivatives for the Gal/GalNAc receptor of rat hepatocytes and peritoneal macrophages. J. Drug Target. 6:201–205 (1998).
H. Kaltner and B. Stierstorfer. Animal lectins as cell adhesion molecules. Acta Anat. 161:162–179 (1998).
D. Gupta, H. Kaltner, X. Dong, H.-J. Gabius, and C. F. Brewer. Comparative crosslinking activity of lactose-specific plant and animal lectins and a natural lactose-binding immunoglobulin G fraction from human serum with asialofetuin. Glycobiology 6:843–849 (1996).
A. Kichler and F. Schuber. Versatile synthesis of bi-and tri-antennary galactose ligands: Interaction with the Gal/GalNAc receptor human hepatoma cells. Glycoconjugate J. 12:275–281 (1995).
H.-J. Gabius. Influence of type of linkage and spacer on the interaction of β-galactoside-binding proteins with immobilized affinity ligands. Anal. Biochem. 189:91–94 (1990).
S. André, S. Kojima, N. Yamazaki, C. Fink, H. Kaltner, K. Kayser, and H.-J. Gabius. Galectins-1 and-3 and their ligands in tumor biology. J. Cancer Res. Clin. Oncol. 125:461–474 (1999).
S. André, P. J. C. Ortega, M. A. Perez, R. Roy, and H.-J. Gabius: Lactose-containing starburst dendrimers: Influence of dendrimer generation and binding-site orientation of receptors (plant/animal lectins and immunoglobulins) on binding properties. Glycobiology 9:1253–1261 (1999).
S. Gabius, S. S. Joshi, H.-J. Gabius, and J. G. Sharp. Establishment, characterization and determination of cell surface sugar receptor (lectin) expression by neoglycoenzymes of a human myeloid marker-expressing B-lymphoblastoid cell line. Anticancer Res. 11:793–800 (1991).
J. Frese Jr., C. H. Wu, and G. Y. Wu. Targeting of genes to the liver with glycoprotein carriers. Adv. Drug Deliv. Rev. 14:137–152 (1994).
J. J. Hangeland, J. T. Lewis, Y. C. Lee, and P. O. P. Ts'o. Celltype specific and ligand specific enhancement of cellular uptake of oligodeoxynucleoside methylphosphonates covalently linked with a neoglycopeptide, YEE(ah-GalNAc)3. Bioconjugate Chem. 6:695–701 (1995).
J.-S. Remy, A. Kichler, V. Mordvinov, F. Schuber, and J.-P. Behr. Targeted gene transfer into hepatoma cells with lipopolyaminecondensed DNA particles presenting galactose ligands: A stage towards artificial viruses. Proc. Natl. Acad. Sci. USA 92:1744–1748 (1995).
D. Yi, R. T. Lee, P. Longo, E. T. Boger, Y. C. Lee, W. A. Petri Jr., and R. L. Schnaar. Substructural specificity and polyvalent carbohydrate recognition by the Entamoeba histolytica and rat hepatic N-acetylgalactosamine/galactose lectins. Glycobiology 8:1037–1043 (1998).
R. T. Lee, Y. Ichikawa, H. J. Allen, and Y. C. Lee. Binding characteristics of galactoside-binding lectin (galaptin) from human spleen. J. Biol. Chem. 265:7864–7871 (1990).
R. T. Lee, H.-J. Gabius, and Y. C. Lee. Ligand binding characteristics of the major mistletoe lectin. J. Biol. Chem. 267:23722–23727 (1992).
H.-J. Gabius. The how and why of protein-carbohydrate interaction: a primer to the theoretical concept and a guide to application in drug design. Pharm. Res. 15:23–30 (1998).
R. T. Lee and Y. C. Lee. Preparation of cluster glycosides of N-acetylgalactosamine that have subnanomolar binding constants towards the mammalian hepatic Gal/GalNAc-specific receptor. Glycoconjugate J. 4:317–328 (1987).
R. T. Lee and Y. C. Lee. Facile synthesis of a high-affinity ligand for mammalian hepatic lectin containing terminal N-acetylgalactosamine residues. Bioconjugate Chem. 8:762–765 (1997).
S.-i. Iida, K. Yamamoto, and T. Irimura. Interaction of human macrophage C-type lectin with O-linked N-acetylgalactosamine residues on mucin glycopeptides. J. Biol. Chem. 274:10697–10705 (1999).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
André, S., Frisch, B., Kaltner, H. et al. Lectin-Mediated Drug Targeting: Selection of Valency, Sugar Type (Gal/Lac), and Spacer Length for Cluster Glycosides as Parameters to Distinguish Ligand Binding to C-Type Asialoglycoprotein Receptors and Galectins. Pharm Res 17, 985–990 (2000). https://doi.org/10.1023/A:1007535506705
Issue Date:
DOI: https://doi.org/10.1023/A:1007535506705