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Angiotensin (1-7) (Ang-(1-7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues - among them, skeletal muscle - by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1-7) carrier. Bioinformatics analysis showed that the Ang-(1-7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1-7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1-7)/PAMAM-OH complex, but not Ang-(1-7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1-7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1-7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1-7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1-7)/PAMAM-OH complex is an efficient delivery method for Ang-(1-7), since it improves the anti-atrophic activity of this peptide in skeletal muscle.

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. Dendrimers are attractive polymers with a well-defined structure and multivalent terminal groups. We have designed a novel type of peptidomimetic based on dendrimer by modifying the amino acids at the periphery of the dendrimer. The dendritic peptidomimetic containing Pro and Arg was bound to a model protein, amphiphysin II SH3 domain, at a similar level to a model binding peptide, a Pro-rich sequence of dynamin.