A luminescent ATCUN peptide variant with enhanced properties for copper(II) sensing in biological media

The measurement of labile Cu^II in biological samples is fundamental for understanding Cu metabolism and has been emerging as a promising diagnostic marker for Cu-related pathologies such as Wilson's and Alzheimer's diseases. The use of fluorescent chelators may be useful to circumvent separation steps employed by current methods. For this purpose, we recently designed a selective and suited-affinity turn-off luminescent probe based on a peptide bearing the Cu^II-binding Xxx-Zzz-His (Amino-Terminal Cu^II- and Ni^II-binding, ATCUN) motif and a Tb^III-DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) complex. Here, we present an analogue probe bearing the ATCUN motif variant Xxx-His-His. This probe showed much faster response in biologically-relevant media and higher stability than the previous motif at low pH. These features could be beneficial to the measurement of dynamic Cu^II fluctuations and the application in slightly acidic media, such as urine.