A phosphorylated zinc finger peptide bearing a gadolinium complex for zinc detection by MRI

Abstract

Two zinc finger peptides, namely ZFQD^Ln and ZFQE^Ln (Ln = Tb or Gd), with an appended Ln³⁺ chelate and a phosphoserine able to coordinate the Ln³⁺ ion are presented. The two peptides differ by the amino acid anchorage of the chelate, either aspartate (D) or glutamate (E). Both peptides are able to bind Zn²⁺ and adopt the ββα fold. Interestingly, ZFQE^Tb shows a decrease in sensitized Tb³⁺ luminescence upon Zn²⁺ binding whereas ZFQD^Tb does not. The luminescence change upon Zn²⁺ binding is attributed to a change in hydration number (q) of the Tb³⁺ ion due to the decoordination of the phosphoserine from the Ln³⁺ ion upon Zn²⁺ binding and peptide folding. This process is highly sensitive to the length of the linker between the Ln chelate and the peptidic backbone. The magnetic properties of the gadolinium analogue ZFQE^Gd were studied. An impressive relaxivity increase of 140% is observed at 60 MHz and 25 °C upon Zn²⁺ binding. These changes can be attributed to a combined increase effect of the hydration number of Gd³⁺ and of the rigidity of the system upon Zn²⁺ binding. Phantom MR images at 9.4 T show a clear signal enhancement in the presence of Zn²⁺. These zinc finger peptides offer a unique platform to design such Zn-responsive probes.