Cu(II), Zn(II) and Ni(II) Binding Studies of a Series of Analog Methanobactin Peptides

Document Type


Degree Name

Master of Science (MS)



Date of Award

Summer 2014


Understanding which structural features of small oligopeptides are important for controlling Cu(II), Zn(II) and Ni(II) binding selectivity and the reduction of Cu(II) --> Cu(I) is potentially useful for developing therapeutics for degenerative diseases where Zn and Cu homeostasis is a contributing factor. Methanobactins (Mbs) are a family of copper-binding natural products involved in copper uptake by methanotrophic bacteria. The Mbs that have been structurally characterized feature copper coordination by two nitrogen-containing oxazolone heterocycles next to enethiol groups embedded in a peptidic backbone of varying composition. The zinc-finger Zif268 specific coordination of Zn(II) via Cys2-His2 ligation provides structural functionality of Zif268. Based on Mbs and Zif268 binding motifs, the metal ion binding properties of the four model oligopeptides ac-His1-Cys2-Gly3-Pro4-His5-Cys6, ac-His1-Cys2-Tyr3-Pro4-His5-Cys6, ac-His1-Cys2-Gly3-Tyr4-Pro5-His6-Cys7 and His1-Cys2-Gly3-Tyr4-Pro5-His6-Cys7 were studied using three different methodologies and have been adopted in order to explore metal binding and redox properties using ultraviolet-visible spectrophotometry (UV-Vis), ion mobility-mass spectrometry (IM-MS) and quantum computation (B3LYP) density functional theory and (LanL2DZ) basis set with the SMD aqueous solvent model. The binding properties of ac-His1-Cys2-Gly3-Pro4-His5-Cys6 has been examined for their binding affinity towards a series of important biologically active metal ions Mn2+, Fe2+, Fe3+, Ni2+, Cu2+, Cu+ and Zn2+. The B3LYP geometry optimization and frequency calculations predict that ac-His1-Cys2-Gly3-Pro4-His5-Cys6 binds to the metal ions, in the aqueous-phase, in the order of Ni2+> Fe3+> Fe2+> Cu2+> Cu+> Zn2+> Mn2+. Tetrahedral and square pyramidal coordination were observed predominantly depending on the charge state of ac-His1-Cys2-Gly3-Pro4-His5-Cys6.


Laurence A. Angel

Subject Categories

Chemistry | Physical Sciences and Mathematics