Synthesis of glycodendrimers by modification of poly(propylene imine) dendrimers

Abstract

The use of preformed poly-(propylene imine) dendrimers (DAB-dendr- (NH2)(x)) for the rapid and facile construction of high molecular weight carbohydrate-coated dendrimers (glycodendrimers) is presented. An efficient attachment of spacer-armed derivatives of D-galactose and lactose to the primary amino end groups of DAB-dendr (NH2)(x) has been achieved by means of amide bond formation, using the N-hydroxysuccinimide coupling procedure. Acetate protecting groups have been employed in order to avoid side reactions at the coupling stage. Deacetylation leads to the target glycodendrimers. The reactivity of all the available DAB dendr-(NH2)(x) (generations 1-5) has been investigated and a series of homologous carbohydratecoated dendrimers have been synthesized. In addition, the attachment of larger saccharide moieties has been demonstrated by the condensation of a trisgalactoside cluster with DAB-dendr-(NH2)(x) carrying both four and eight primary amino groups. The regularity of the glycodendrimers has been proven by NMR spectroscopy, and the molecular weights of the low-generation carbohydrate-coated dendrimers have been determined by mass spectrometry. Modifications of DAB dendr (NH2)(x) with biologically active carbohydrates affords a new and simple approach to high molecular weight tom pounds that may be considered as neoglycoconjugates with perfectly symmetrical structures and that offer much promise as multivalent ligands involved in carbohydrate protein interactions.