Site–site interactions within high-loading PAMAM dendrimer resin beads

Combinatorial chemistry and solid-phase synthesis have revolutionised the process of drug discovery in the last decade. Ever since the concept of split and mix synthesis was introduced in 1988, and in particular the concept of one bead one compound, this approach has been associated with the possibility of generating thousands or millions of compounds in only a relatively small number of synthetic steps. The demand for high loading resins has therefore increased over the last few years. Our research has focussed on bead-loading enhancement via a dendrimerisation process. Dendrimer resin beads have shown compatibility for many chemical conditions, however high functional group density could produce undesirable site–site interactions.