Metal-peptide complexes - a novel class of molecular receptors for electrochemical phosphate sensing

Determination of phosphate anions concentration in body fluids provides information about various disorders such as hyperparathyroidism or vitamin D deficiency. Therefore, the monitoring of phosphates level is of interest for human health. Chemical sensors are a good alternative to classic analytical methods, but their construction requires the synthesis of appropriate receptors selectively binding the analyte.

Amyloid β peptides (Aβ) related to Alzheimer’s Disease are well known for their neurotoxic properties. However, their N-terminally truncated analogs own unique coordination properties that could be employed in the design of potential receptors for biorelevant anionic species. The Aβ_5-9 peptide possesses a His-2 binding motif and thus forms stable complexes with transition metal ions, where metal ion such as Cu(II) or Ni(II) is bound by three nitrogen (3N) from the His residue, the N-terminal amine, and the peptide backbone amide. The resulting chelates exhibit high stability and a labile coordination site enabling ternary interactions. Furthermore, metal-peptide complexes offer the possibility of fine-tuning their sensitivity and selectivity for desired applications by altering the amino acid sequence and metal ion center.

The present work explores and compares the coordination and redox properties of Aβ_5-9 complexes with Cu(II) and Ni(II) ions using electrochemical and spectroscopic techniques. The ability of binding biologically relevant phosphate anions and nucleotides by metal-peptide complexes was also studied. Obtained results provided a new insight into the design of a promising class of peptide-based molecular receptors with potential application as recognition elements in electrochemical biosensors and in vitro clinical diagnostics.

Acknowledgments: This work has been financially supported by the Warsaw University of Technology under the program Excellence Initiative, Research University (ID-UB), BIOTECHMED-1 project no. PSP 504/04496/1020/45.010407 and implemented as a part of the Operational Program Knowledge Education Development 2014-2020 (Project No POWR.03.02.00-00-I007/16-00) co-financed by the European Social Fund.