DNA Cleaving "Tandem-Array" Metallopeptides Activated With KHSO₅: Towards the Development of Multi-Metallated...

Area of Science:

• Biochemistry
• Bioinorganic Chemistry
• Peptide Chemistry

Background:

• Gly-Gly-His peptides introduce metal binding and redox activity into biomolecules.
• Native Gly-Gly-His metal binding requires a terminal amine ligand.
• Ornithine substitution enables solid-phase synthesis and side-chain metal binding.

Purpose of the Study:

• To create tandem arrays of Gly-Gly-His-like metal binding units in linear peptides.
• To investigate the metal binding properties of these tandem arrays.
• To evaluate their efficacy in oxidative DNA modification.

Main Methods:

• Solid-phase peptide synthesis utilizing ornithine substitution.
• Synthesis of peptides with the general form NH2-Gly-Gly-His-[(δ)-Orn-Gly-His]n-(δ)-Orn-Gly-His-CONH2 (n=0, 1, 2).
• Metal binding titrations monitored by UV-vis and ESI-MS.
• Assessment of oxidative DNA modification activity.

Main Results:

• Successfully synthesized tandem arrays of Gly-Gly-His-like metal binding units.
• Demonstrated that these arrays bind Cu2+, Ni2+, or Co2+ at each available metal binding site.
• Observed enhanced oxidative DNA modification compared to parent M(II)•Gly-Gly-His complexes.

Conclusions:

• Tandem array metallopeptides can be efficiently assembled using ornithine substitution.
• These novel metallopeptides exhibit multi-metal binding capabilities.
• The enhanced oxidative DNA modification suggests potential as "next generation" bioactive compounds.