Synthesis of L-Dopa Modifier L-Dopa-L-His and its Interaction with DNA

Though L-dopa is an effective drug for Parkinson’s disease, the usage of L-dopa in clinical treatment is limited for its physico-chemical properties which affect the bioavailability of L-dopa and increase the side effects of L-dopa. For improving the availability of L-dopa, L-dopa-L-His was synthesized by Fmoc solid-phase peptide synthesis, purified by reversed-phase HPLC and characterized by using 1H, 13C NMR and ESI-MS. The interaction of L-dopa-L-His and L-dopa with ctDNA has been investigated respectively by UV absorption and fluorescence spectroscopy. The results indicated that both L-dopa and L-dopa-L-His interacted with ctDNA through intercalative mode. The binding constant of L-dopa and Ldopa- L-His with ctDNA were 4.99x1010 L·mol-1·s-1 and 8.25x1011 L·mol-1·s-1, which showed a higher affinity of L-dopa- L-His to DNA for the imidazole side-chain. Meanwhile, compared with the free L-dopa, gel electrophoresis assay also demonstrated that the L-dopa-L-His interacted with plasmid DNA by stronger intercalation.