Chemistry
Document Type
Article
Abstract
Copper is an essential trace metal for biological processes in humans and animals. A low level of copper detection at physiological pH using fluorescent probes is very important for in vitro applications, such as the detection of copper in water or urine, and in vivo applications, such as tracking the dynamic copper concentrations inside cells. Copper homeostasis is disrupted in neurological diseases like Alzheimer’s disease, and copper forms aggregates with amyloid beta (Ab42) peptide, resulting in senile plaques in Alzheimer’s brains. Therefore, a selective copper detector probe that can detect amyloid beta peptide-copper aggregates and decrease the aggregate size has potential uses in medicine. We have developed a series of Cu2+-selective low fluorescent to high fluorescent tri and tetradentate dentate ligands and conjugated them with a peptide ligand to amyloid-beta binding peptide to increase the solubility of the compounds and make the resultant compounds bind to Cu2+–amyloid aggregates. The copper selective compounds were developed using chemical scaffolds known to have high affinity and selectivity for Cu2+, and their conjugates with peptides were tested for affinity and selectivity towards Cu2+. The test results were used to inform further improvement of the next compound. The final Cu2+ chelator–peptide conjugate we developed showed high selectivity for Cu2+ and high fluorescence properties. The compound bound 1:1 to Cu2+ ion, as determined from its Job’s plot. Fluorescence of the ligand could be detected at nanomolar concentrations. The effect of this ligand on controlling Cu2+–Ab42 aggregation was studied using fluorescence assays and microscopy. It was found that the Cu2+–chelator–peptide conjugate efficiently reduced aggregate size and, therefore, acted as an inhibitor of Ab42-Cu2+ aggregation. Since high micromolar concentrations of Cu2+ are present in senile plaques, and Cu2+ accelerates the formation of toxic soluble aggregates of Ab42, which are precursors of insoluble plaques, the developed hybrid molecule can potentially serve as a therapeutic for Alzheimer’s disease.
Publication Title
Biosensors
Publication Date
5-2024
Volume
14
Issue
5
ISSN
2079-6374
DOI
10.3390/bios14050247
Keywords
Cu-amyloid beta, fluorescent copper chelator, non-amyloid aggregate inhibition
Repository Citation
Nguyen, Ngoc Kim; Poduska, Bella; Franks, Mia; Bera, Manoranjan; MacCormack, Ian; Lin, Guoxing; Petroff, Alexander P.; Das, Samir; and Nag, Arundhati, "A Copper-Selective Sensor and Its Inhibition of Copper-Amyloid Beta Aggregation" (2024). Chemistry. 33.
https://commons.clarku.edu/chemistry/33
Cross Post Location
Student Publications
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright Conditions
Published source must be acknowledged with citation: Nguyen, N. K., Poduska, B., Franks, M., Bera, M., MacCormack, I., Lin, G., ... & Nag, A. (2024). A Copper-Selective Sensor and Its Inhibition of Copper-Amyloid Beta Aggregation. Biosensors, 14(5), 247.