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 synthetic compounds with significant biomedical potential. In this study, we report the chemical synthesis, structural characterization and evaluation of the antioxidant activity of two synthetic quinazoline-derived 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 affinities with both dsDNA and BSA. Our results suggest that the artificial amino acids presented herein can modulate the secondary structure of both DNA and serum albumin, highlighting their potential as molecular tools in biomedical research. Furthermore, we provide evidence that synthetic-derived amino acids exhibit protective potential against oxidative damage induced by various sources, possibly including harmful environmental synthetic derivatives, by demonstrating significant antioxidant activity, as confirmed through our DPPH assays. This work expands the understanding of synthetic–biomacromolecule interactions and supports the role of non-natural amino acids as modulators of nucleic acids and proteins in therapeutic contexts and as antioxidants.