Biomacromolecular interactions and antioxidant properties of novel synthetic amino acids targeting DNA and serum albumin
Artificial amino acids, by virtue of their non-natural origin and metabolic stability, can be regarded as true synthetics with significant biomedical potential. In this study, we report the chemical synthesis, the structural characterization and the antioxidant activity evaluation of two synthetic amino acids capable of interacting with biological macromolecules such as double-stranded DNA (dsDNA) and serum albumins. Using calf thymus DNA and bovine serum albumin (BSA) as model systems, we investigated the binding properties and structural effects of these derivatives through a multidisciplinary experimental approach. The study combines synthetic chemistry with analytical and spectroscopic techniques, primarily circular dichroism (CD) spectroscopy, to monitor conformational changes induced in dsDNA and BSA upon peptide binding, while CD spectral deconvolution provided mechanistic insights into the mode of interaction between the synthetic amino acids and their biological target. Additionally, molecular docking simulations were employed to explore potential binding sites and interaction energies with both dsDNA and BSA. Our results suggest that these artificial amino acids can significantly modulate the secondary structure of both DNA and serum albumin, highlighting their potential as molecular tools in biomedical research. Furthermore, we provide the first evidence that synthetic-derived amino acids exhibit protective potential against oxidative damage induced by various sources, possibly including harmful environmental synthetics, by demonstrating significant antioxidant activity, as confirmed through our DPPH assays. This work expands the understanding of synthetic–biomacromolecule interactions and underscores the promise of non-natural amino acids as modulators of nucleic acids and proteins in therapeutic contexts and as antioxidants.