Abstract: Previously, it was shown that a new bioactive tetrapeptide Ala-Glu-Asp-Leu (AEDL) can modulate gene expression and promote normalization of lung function. In this work, we use the molecular dynamics (MD) method to simulate the interaction of this tetrapeptide molecules with a nanocontainer based on a lysine dendrimer with arginine-histidine (RH) and histidine-arginine (HR) spacers. Since the charge of the histidine amino acid residue (His, H) in the dendrimer depends on pH, we performed MD simulations of the complexation of AEDL molecules with these two dendrimers at two different pH values. It was found that all the studied dendrimers are able to carry a large number (from 14 to 16) of AEDL molecules at both pH values. Tetrapeptides form more hydrogen bonds with dendrimers having protonated histidines (at lower pH) and penetrate them deeper compared to dendrimers with neutral histidines. This leads to an increase in the capacity of the dendrimer carrier for transferring guest molecules by approximately 8%. The obtained data can be used to select the most suitable dendrimer for delivery of the AEDL tetrapeptide.

Keywords: Peptide dendrimers, oligopeptides, complexes, MD simulation, nanocontainer, drug delivery

Pages: 469-477