Using Native Chemical Ligation for Site-Specific Synthesis of Hetero-bis-lanthanide Peptide Conjugates: Application to Ratiometric Visible or Near-Infrared Detection of Zn2+

The interest in ratiometric luminescent probes that detect and quantify a specific analyte is growing. Owing to their special luminescence properties, lanthanide(III) cations offer attractive opportunities for the design of dual-color ratiometric probes. Here, the design principle of hetero-bis-lanthanide peptide conjugates by using native chemical ligation is described for perfect control of the localization of each lanthanide cation within the molecule. Two zinc-responsive probes,r-LZF1(Tb|Cs124|Eu)andr-LZF1(Eu|Cs124|Tb)are described on the basis of a zinc finger peptide and two DOTA (DOTA=1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid) complexes of terbium and europium. Both display dual-color ratiometric emission in response to the presence of Zn2+. By using a screening approach, anthracene was identified for the sensitization of the luminescence of two near-infrared-emitting lanthanides, Yb(3+)and Nd3+. Thus, two novel zinc-responsive hetero-bis-lanthanide probes,r-LZF3(Yb|Anthra|Nd)andr-LZF3(Nd|Anthra|Yb)were assembled, the former offering a neat ratiometric response to Zn(2+)with emission in the near-infrared around 1000 nm, which is unprecedented.