14563-31-6Relevant academic research and scientific papers
Amphiphilic Distyrylbenzene Derivatives as Potential Therapeutic and Imaging Agents for Soluble and Insoluble Amyloid β Aggregates in Alzheimer's Disease
Arango, Andres S.,Bandara, Nilantha,Cho, Hong-Jun,Huang, Yiran,Huynh, Truc T.,Mirica, Liviu M.,Rogers, Buck E.,Sen, Soumyo,Sun, Liang,Tajkhorshid, Emad
, p. 10462 - 10476 (2021)
Alzheimer's Disease (AD) is the most common neurodegenerative disease, and efficient therapeutic and early diagnostic agents for AD are still lacking. Herein, we report the development of a novel amphiphilic compound, LS-4, generated by linking a hydrophobic amyloid-binding distyrylbenzene fragment with a hydrophilic triazamacrocycle, which dramatically increases the binding affinity toward various amyloid β (Aβ) peptide aggregates, especially for soluble Aβ oligomers. Moreover, upon the administration of LS-4 to 5xFAD mice, fluorescence imaging of LS-4-treated brain sections reveals that LS-4 can penetrate the blood-brain barrier and bind to the Aβ oligomers in vivo. In addition, the treatment of 5xFAD mice with LS-4 reduces the amount of both amyloid plaques and associated phosphorylated tau aggregates vs the vehicle-treated 5xFAD mice, while microglia activation is also reduced. Molecular dynamics simulations corroborate the observation that introducing a hydrophilic moiety into the molecular structure of LS-4 can enhance the electrostatic interactions with the polar residues of the Aβ species. Finally, exploiting the Cu2+-chelating property of the triazamacrocycle, we performed a series of imaging and biodistribution studies that show the 64Cu-LS-4 complex binds to the amyloid plaques and can accumulate to a significantly larger extent in the 5xFAD mouse brains vs the wild-type controls. Overall, these results illustrate that the novel strategy, to employ an amphiphilic molecule containing a hydrophilic moiety attached to a hydrophobic amyloid-binding fragment, can increase the binding affinity for both soluble and insoluble Aβ aggregates and can thus be used to detect and regulate various Aβ species in AD.
Rational design of amyloid binding agents based on the molecular rotor motif
Sutharsan, Jeyanthy,Dakanali, Marianna,Capule, Christina C.,Haidekker, Mark A.,Yang, Jerry,Theodorakis, Emmanuel A.
scheme or table, p. 56 - 60 (2010/11/02)
New fluorescent probes, designed based on the molecular rotor motif, displayed good affinity for aggregated b-amyloid peptides. The physical and fluorescence properties of these probes can be fine tuned by modifying their chemical structures. These findin
