Dendritic galactosides based on a beta-cyclodextrin core for the construction of site-specific molecular delivery systems: synthesis and molecular recognition studies

Chemistry. 2002 Feb 15;8(4):812-27. doi: 10.1002/1521-3765(20020215)8:4<812::aid-chem812>3.0.co;2-p.

Abstract

In order to evaluate the ability of multivalent glycosides based on a beta-cyclodextrin core as site-specific molecular carriers, a study on both the inclusion complexation behaviour and lectin binding affinity of branched and hyperbranched beta-cyclodextrins is presented. A series of cluster galactosides constructed on beta-cyclodextrin scaffolds containing seven 1-thio-beta-lactose or beta-lactosylamine bound to the macrocyclic core through different spacer arms were synthesised. In addition, the first synthesis of three first-order dendrimers based on a beta-cyclodextrin core containing fourteen 1-thio-beta-D-galactose, 1-thio-beta-lactose and 1-thio-beta-melibiose residues was performed. Calorimetric titrations performed at 25 degrees C in buffered aqueous solution (pH 7.4) gave the affinity constants and the thermodynamic parameters for the complex formation of these beta-cyclodextrin derivatives with guests sodium 8-anilino-1-naphthalenesulfonate (ANS) and 2-naphthalenesulfonate, and lectin from peanut (Arachis hypogaea) (PNA). The persubstitution of the primary face of the beta-cyclodextrin with saccharides led to a slight increase of the binding constant values for the inclusion complexation with ANS relative to the native beta-cyclodextrin. However, the increase of the steric congestion due to the presence of the saccharide residues on the narrow rim of the beta-cyclodextrin may cause a decrease of the binding ability as shown for sodium 2-naphthalenesulfonate. The spacer arms are not passive elements and influence the host binding ability according to their chemical nature. PNA forms soluble cross-linked complexes with cluster galactosides and lactosides scaffolded on beta-cyclodextrin but not with cluster galactopyranosylamines or melibiose. Both, perbranched and hyperbranched beta-cyclodextrins, form stronger complexes with PNA than the monomeric analogues. However, the use of hyperbranched CDs does not contribute to the improvement of the complex stability relative to heptakis-glycocyclodextrin derivatives. Finally, a titration experiment with PNA and a complex formed by a heptakis lactose beta-cyclodextrin derivative with sodium 2-naphthalenesulfonate showed the formation of a soluble cross-linked complex with stronger affinity constant and higher stoichiometry than those observed for the complex formation of PNA with the same heptakis-lactose beta-cyclodextrin derivative, suggesting the formation of a three component complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilino Naphthalenesulfonates / metabolism
  • Arachis / chemistry
  • Binding Sites
  • Calorimetry
  • Cyclodextrins / chemistry
  • Drug Delivery Systems / methods*
  • Galactosides / chemical synthesis*
  • Galactosides / metabolism
  • Lectins / metabolism
  • Naphthalenesulfonates / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thermodynamics
  • Titrimetry
  • beta-Cyclodextrins*

Substances

  • Anilino Naphthalenesulfonates
  • Cyclodextrins
  • Galactosides
  • Lectins
  • Naphthalenesulfonates
  • beta-Cyclodextrins
  • 1-anilino-8-naphthalenesulfonate
  • betadex