SCAN: Synthesis and study of new selective Copper (I) cyclodecapeptide chelators for Wilson Disease type

ITQB Scan Seminar

Title : Synthesis and study of new selective Copper (I) cyclodecapeptide chelators for Wilson Disease type.

Speaker: Anaïs Pujol

Affiliation: Bioinorganic Chemistry and Peptide Design Laboratory

Abstract: Copper is an essential trace element which forms an integral component of many enzymes, but while trace amounts of copper are needed to sustain life, excess copper is extremely toxic (Fenton type reaction). Copper concentration is extremely regulated by proteins which carrier it and excrete it. Wilson disease is a genetic autosomal recessive disorder of copper transport, characterized by defective biliary copper excretion and resulting in copper accumulation, primarily in the liver but also in brain and cornea. Wilson disease occurs worldwide with an average prevalence of ~30 affected individuals per million population and symptoms at any age are frequently no specific. Treatments for Wilson disease have concentrated on the use of chelators to reduce copper intestinal absorption and to promote its excretion by urine. They do not target liver, the first organ affected, and they are few copper selective. Nowadays, no treatments take over excess copper of liver so a molecule which could capture copper of the liver will be fine to alleviate patients. Thus, we design new vectors which consist of two units: one targetting liver and the second chelating copper(I). The chelating unit exhibits a strong affinity for copper(I) and a good selectivity Cu+/Zn2+.
Two chelators models on two or three cysteines-based were realized as well as the physicochemical characterization of their metal complexes with copper and other divalents cations d10. Then, the vectorization of these models was done as well as cellular tests to evaluate the availability of vectors to complex intracellular copper concentration.

Keys words: Copper(I), Wilson Disease, chelators, liver, asialoglycoproteins