10.1039/b905938e
The research investigates the creation and binding affinity of multivalent ligands for the Syk tandem SH2 domain using ITAM-derived phosphopeptides attached to dendrimers. The purpose is to enhance the binding affinity of these ligands through multivalency, which could have therapeutic implications for conditions like allergic responses. The researchers synthesized a series of dendrimers with varying valencies (from monovalent to octavalent) by attaching a tetrapeptide sequence (pTyr-Glu-Thr-Leu) from the ITAM motif to dendrimers using 'click' chemistry. The binding affinity of these dendrimers for Syk tSH2 was assessed via surface plasmon resonance (SPR) competition experiments. The study found that tetravalent and octavalent dendrimers exhibited a significant multivalency effect, with affinities in the high nanomolar range, approximately 100-fold enhanced compared to the monovalent tetrapeptide. The key chemicals used include the ITAM-derived phosphopeptide, various generations of dendrimers, copper(I) sulfate, sodium ascorbate for the 'click' chemistry, and Syk tSH2 for binding assays. The conclusion is that multivalency significantly enhances the binding affinity, and further improvements might be achieved by optimizing the orientation of the phosphopeptides on the dendrimers.