Abstract
This paper compares covalent and non-covalent approaches for the organisation of ligand arrays to bind integrins. In the covalent strategy, linear RGD peptides are conjugated to first and second generation dendrons, and using a fluorescence polarisation competition assay, the first generation compound is demonstrated to show the most effective integrin binding, with an EC50 of 125 mu M (375 mu M per peptide unit). As such, this dendritic compound is significantly more effective than a monovalent ligand, which does not bind integrin, even at concentrations as high as 1 mM. However, the second generation compound is significantly less effective, demonstrating that there is an optimum ligand density for multivalency in this case. In the non-covalent approach to multivalency, the same RGD peptide is functionalised with a hydrophobic C12 chain, giving rise to a lipopeptide which is demonstrated to be capable of self-assembly. This lipopeptide is capable of effective integrin binding at concentrations of 200 mu M. These results therefore demonstrate that covalent (dendritic) and non-covalent (micellar self-assembly) approaches have, in this case, comparable efficiency in terms of achieving multivalent organisation of a ligand array.
| Original language | English |
|---|---|
| Pages (from-to) | 4795-4801 |
| Number of pages | 7 |
| Journal | Organic and Biomolecular Chemistry |
| Volume | 9 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - 7 Jul 2011 |
Keywords
- GENE DELIVERY
- CELL-ADHESION
- ALPHA(V)BETA(3) ANTAGONISTS
- SUPRAMOLECULAR CHEMISTRY
- BIOLOGICAL EVALUATION
- SIGNAL-TRANSDUCTION
- ENDOTHELIAL-CELLS
- CASCADE POLYMERS
- DRUG-DELIVERY
- DNA-BINDING