Synthesis, characterization of Cu(II) and Zn(II) complexes of proline-glycine and proline-leucine tetrapeptides: In vitro DNA binding and cleavage studies

Abstract

New Cu(II) and Zn(II)-based peptide solid complexes 1-4 were designed by de novo synthetic strategy from tetrapeptide ligands, Pro-Gly-Pro-Gly, L 1/Pro-Leu-Pro-Leu, L 2 and thoroughly characterized by various spectroscopic techniques. To confirm the stability of peptide complexes in solution, solution stability studies of 1 and 3 over a pH range 2-12 were carried out which revealed no change in absorption or intensity of bands. In vitro DNA binding studies employing various optical techniques were carried out to examine the propensity of complexes towards CT DNA. The results of corroborative experiments reveal that the complexes avidly bind to CT DNA via groove binding, with highest K b values for 1 indicative of strong binding propensity as compared to ligands and 2-4. To compare the binding affinity for nucleotides, UV-Vis titrations of 1 and 2 with 5′-GMP and 5′-TMP were carried out; further validated by 1H and 31P NMR. The supercoiled pBR322 DNA nuclease activity 1 and 2, demonstrated that both the complexes were capable of cleaving DNA but with striking differences in their nuclease activity; Cu(II) complex cleaved DNA through oxidative cleavage while Zn(II) complex followed hydrolytic cleavage pathway. © 2012 Elsevier B.V. All rights reserved.