Design, synthesis and biological evaluation of peptide dendrimers with wound healing promoting activity

Abstract

Peptide dendrimers are tree-like macromolecules composed of a peptidyl branching core and/or covalently attached surface functional units. Owing to their multimeric nature and unambiguous composition, peptide dendrimers show several significant advantages over single peptides, such as amplification of function, biocompatibility and water-solubility. Thus, dendrimer-based strategies are widely used for designing peptide agents. Using this strategy, we have designed and synthesized a series of wound healing-promoting peptide dendrimers and their efficacy was evaluated on wounded diabetic mice. The results showed that all dendrimers have wound healing promoting effects, while tetramers showed superior activity to others. Treatment with the dendrimers of AK14, AK21, and AK22 resulted in a smaller wound area percentage than any others on the 7th, 9th, and 11th days. Moreover, hemolysis assay suggested all dendrimers except AK22, AK23, and AK31 have little hematotoxicity, even at 512 μg/mL. In vitro plasma stability assay also showed an increased stability of AK21 when comparing with its parent compound. Therefore, we suggest the dendrimer-based strategy has potential for designing wound healing-promoting peptides.