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A probe for the selective detection of copper diseases

Researchers at our Chemistry and Biology of Metals Laboratory have developed a selective probe inspired by a protein selectively carrying Cu+ in bacteria. This probe, made luminescent by a grafted terbium complex, is very sensitive and perfectly Cu+ selective by not responding to any other physiological ion.

Published on 26 January 2016
Although essential for life, copper can become toxic if it accumulates in the body. Its elimination by liver cells is inadequate in people with Wilson's disease, a genetic condition that affects 1:30,000 to 100,000 every year in France. Conversely, people with Menkes syndrome, a rarer genetic condition, have a deficient copper metabolism and suffer progressive neurodegeneration, often associated with a poor prognosis. Measuring copper levels in the body is a major diagnostic tool to detect these pathologies at an earlier stage and provide more targeted care.

"There aren't many easy-to-use, direct techniques for measuring copper levels," said Chemistry and Biology of Metals Laboratory scientist Olivier Sénèque. "We have developed a new technique for copper detection inspired by a copper-binding protein present in some bacteria." These are gram- negative bacteria, such as Salmonella or Escherichia coli. They contain a protein called CusF which is responsible for copper transport. These copper transporters allow bacteria to eliminate excess copper. "They differ from other bacteria by the fact that they incorporate tryptophan, an amino acid which, under ultraviolet (UV) light, is capable of exciting lanthanides which, in turn, emit visible light," the scientist said. With this in mind, the scientists from our institut and CEA-INAC have developed a system composed, in particular, of tryptophan and terbium (a lanthanide), that attracts copper, just like CusF. This fluorescence system triggers a domino effect: (a) the probe traps the copper, (b) the tryptophan contained in the probe is excited, (c) the terbium, also contained in the probe, is in turn excited and emits green light. "Our result is the basic design of a new probe that can evaluate the copper levels in a cell," Olivier Sénèque outlines. "Now we are seeking to replace the tryptophan with a compound that is more suitable for fluorescence microscopy studies of living cells, with slightly shifted excitation and emission for easier detection."
The lanthanides are metal ions belonging to the family of rare earth elements. Some of them are capable of emitting light from the visible to near-infrared, depending on the lanthanide. They are used in the screens of smartphones due to their emission properties, and increasingly, in fluorescence-based biological tests.

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