科研之友
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摘要
The pseudopeptide L, derived from a nitrilotriacetic acid scaffold and functionalized with three histidine moieties, is reminiscent of the amino acid side chains encountered in the Alzheimer's peptide (A). Its synthesis and coordination properties for Cu and Cu are described. L efficiently complex Cu in a square-planar geometry involving three imidazole nitrogen atoms and an amidate-Cu bond. By contrast, Cu is coordinated in a tetrahedral environment. The redox behavior is irreversible and follows an ECEC mechanism in accordance with the very different environments of the two redox states of the Cu center. This is in line with the observed resistance of the Cu complex to oxidation by oxygen and the Cu complex reduction by ascorbate. The affinities of L for Cu and Cu at physiological pH are larger than that reported for the A peptide. Therefore, due to its peculiar Cu coordination properties, the ligand L is able to target both redox states of Cu, redox silence them and prevent reactive oxygen species production by the CuA complex. Because reactive oxygen species contribute to the oxidative stress, a key issue in Alzheimer's disease, this ligand thus represents a new strategy in the long route of finding molecular concepts for fighting Alzheimer's disease.
- 出版日期2017-12-1
- 单位中国地震局
