Mimicry of Dopamine 1 Receptor Signaling with Cell-Penetrating Peptides

In this study, through the use of protein mimicry, a peptide was developed to activate the dopamine 1 receptor signaling pathway from the inside of the cell and in absence of the natural extracellular ligand. The sequence was initially derived from the intracellular interaction site between the activated receptor and the alpha domain of its associated G-protein and subsequently modified to increase its cell-penetrating properties. The peptide was then synthesized via solid phase peptide synthesis, purified and tested on cell models. This novel lipopeptide proved to be capable of efficiently ubiquitously penetrating the cell without the need for transfection agents or chiral recognition by specific pathways. Furthermore, the peptide induced the cellular response normally achieved through the activation of the receptor in cells that had not been treated with the natural ligand. The peptide could work as a candidate substitute to l -DOPA, leading the way for a peptides-based treatment for Parkinson’s disease.