Synthesis and binding properties of peptidomimetics based on a dendritic polymer

Abstract

Dendrimers are attractive polymers with a well-defined structure and multivalent terminal groups. We have designed a novel type of peptidomimetic based on a dendrimer by modifying the amino acids at the periphery of the dendrimer. Alanine- and phenylalanine-bound dendrimers containing different ratios of the two amino acids were synthesized by controlling the reaction ratios. A dendritic peptidomimetic containing proline (Pro) and arginine (Arg) was also synthesized. It has been reported that Pro- and Arg-containing peptides, named Pro-rich peptides, are associated with the src homology 3 (SH3) domain. We have focused on the binding of a Pro-rich peptide of dynamin to the SH3 domain of amphiphysin II as a model case of protein–protein interaction. The dendritic peptidomimetic containing Pro and Arg was found to bind to the SH3 domain to a similar degree as the dynamin Pro-rich peptide, indicating that dendrimers conjugating amino acids can behave as potential peptidomimetics.