Endogenous lectins as targets for drug delivery

To minimize side effects of drugs it would be ideal to target them exclusiv ely to those cell types which require treatment. As a means to this end pro totypical cellular recognition systems pique our interest to devise biomime tic strategies. Since oligosaccharides of glycoconjugates outmatch other in formation-carrying biomolecules (proteins, nucleic acids) in theoretical st orage capacity by far, work on the sugar code can spark off development of effective targeting devices. Conjugation of custom-made glycan epitopes to proteins or biocompatible non-immunogenic polymeric scaffolds produces neog lycoconjugates with purpose-adaptable properties. In the interplay with end ogenous receptors such as lectins, suitable oligosaccharides such as histo- blood group trisaccharides as parts of neoglycoconjugates have already prov en their practical applications in histopathology. Elucidation of the struc ture of cell lectins with currently five main families aids to tailor ligan d characteristics rationally. They include the types of functional groups a nd their topological presentation to optimize the bimolecular binding as we ll as the optimal spatial clustering and spacer characteristics to exploit cooperativity. Indeed, the potent trivalent cluster glycosides designed for the C-type asialoglycoprotein receptors furnish an instructive example how to turn the theoretical guideline on ligand modification into nhl-affinity . By placing emphasis on tissue lectins as targets of neoglycoconjugate-med iated drug delivery, the long-term perspective is opened to likewise test m embers of these families themselves for routing of therapeutic payloads, ai ming at cell addressins. This review illustrates the conceivable potential which work on the sugar code with custom-made neoglycoconjugates and tissue lectins can have in store for drug delivery. (C) 2000 Elsevier Science B.V . All rights reserved.