Lewis, Mark A.Williams, Katie M.Fang, Ya-YinSchultz, Franklin A.Long, Eric C.2016-06-282016-06-282014Lewis, M. A., Williams, K. M., Fang, Y.-Y., Schultz, F. A., & Long, E. C. (2014). DNA Cleaving “Tandem-Array” Metallopeptides Activated With KHSO5: Towards the Development of Multi-Metallated Bioactive Conjugates and Compounds. Current Bioactive Compounds, 10(1), 13–20. http://doi.org/10.2174/1573407210011407241509011573-4072https://hdl.handle.net/1805/10223Amino terminal peptides of the general form Gly-Gly-His have been used to introduce single sites of metal binding and redox activity into a wide range of biomolecules to create bioactive compounds and conjugates capable of substrate oxidation. We report here that Gly-Gly-His-like peptides linked in a tandem fashion can also be generated leading to multi-metal binding arrays. While metal binding by the native Gly-Gly-His motif (typically to Cu(2+), Ni(2+), or Co(2+)) requires a terminal peptide amine ligand, previous work has demonstrated that an ornithine (Orn) residue can be substituted for the terminal Gly residue to allow solid-phase peptide synthesis to continue via the side chain N-δ. This strategy thus frees the Orn residue N-α for metal binding and permits placement of a Gly-Gly-His-like metal binding domain at any location within a linear, synthetic peptide chain. As we show here, this strategy also permits the assembly of tandem arrays of metal binding units in linear peptides of the form: NH2-Gly-Gly-His-[(δ)-Orn-Gly-His]n-(δ)-Orn-Gly-His-CONH2 (where n = 0, 1, and 2). Metal binding titrations of these tandem arrays monitored by UV-vis and ESI-MS indicated that they bind Cu(2+), Ni(2+), or Co(2+) at each available metal binding site. Further, it was found that these systems retained their ability to modify DNA oxidatively and to an extent greater than their parent M(II)•Gly-Gly-His. These findings suggest that the tandem array metallopeptides described here may function with increased efficiency as "next generation" appendages in the design of bioactive compounds and conjugates.en-USPublisher PolicyDNA cleavageGly-Gly-Hismetal binding peptidemetallopeptideArticle