Design of a Peptidic Turn with High Affinity for HgII
Sara Pires, Jelena HabjaniÄ, Murat Sezer, ClÃ¡udio M. Soares, Lars Hemmingsen, and Olga Iranzo
Inorg. Chem., Article ASAP
Publication Date (Web): October 17, 2012
Copyright © 2012 American Chemical Society
A four amino acid peptide containing the Î²-turn template dPro-Pro in the middle and two cysteines (Cys) in the terminal positions (CdPPC) has been synthesized and its mercury(II) coordination properties studied using different spectroscopic methods. The UVâ€“vis, CD, 199mHg PAC, and Raman spectroscopic studies indicate the binding of HgII to the two Cys, forming the dithiolatemercury(II) complex Hg(CdPPC). Electrospray ionization mass spectrometry corroborates the 1:1 complex formation. A log K = 40.0 was determined for the formation constant of the Hg(CdPPC) complex using competition potentiometric studies. Replacement of the dPro-Pro motif by a Pro-Pro unit generated a peptide (CPPC) capable of forming a similar species [Hg(CPPC)] but showing a lower affinity for HgII (at least 3â€“3.5 orders of magnitude lower). The introduction of the dPro-Pro motif is crucial to induce the folding of the CdPPC peptide into a Î²-turn, preorganizing the two Cys for mercury(II) coordination. While the simple dPro-Pro unit mimics the overall preorganization achieved by the protein scaffold in metalloproteins containing the conserved metal ion chelation unit CXXC, the high thiophilicity of this metal stabilizes the final complex in a wide pH range (1.1â€“10). Using computational modeling, the structures of two conformers for Hg(CdPPC) have been optimized that differ mainly in the orientation of the plane containing Sâ€“Hgâ€“S with respect to the anchoring C atoms.