Improving The Performance Of Aβ Protein Fluorescent Probes By Homodimer

Alzheimer’s disease(AD)is a common neurodegenerative disease with an insidious and long latent onset and a complex etiology,and its main clinical symptoms are irreversible memory loss and cognitive deficits,which can impose a heavy burden on patients and their families.Although it is debated whether Aβ protein precedes other AD pathogenic factors,recent evidence still suggests that Aβ protein remains a key pathogenic factor in AD.Early detection of pathological features is important for the early diagnosis and treatment of AD,and the use of fluorescent probe molecular imaging is one of the important tools for early and accurate diagnosis of AD.However,most of the currently reported fluorescent probes and commonly used design strategies have the following drawbacks: 1.Most of the targeting Aβ protein probes are designed based on the intramolecular charge transfer(ICT)luminescence mechanism,and their own background signals are too high and the signal-to-noise ratio is not high,which makes the imaging contrast not high.2.The affinity between the probe and the Aβ protein is low and the kinetic binding process is slow.3.In order to obtain a probe molecule with excellent performance,most screening of structure and functional groups is required,during which some probe molecules were eliminated due to partial shortcomings,which is slightly unfortunate.Based on the above factors,this project proposes to optimize the performance of some Aβprobes by using the homodimer strategy,in order to be able to improve the performance of some probes,and verify the feasibility of this scheme through a series of molecular synthesis and its performance experiments,as follows: homodimer molecules were successfully synthesized based on N,N-dimethylphenylene dyes,which were linked by end-amino alkyl chains.The spectroscopic characterization results showed that the introduction of alkyl chains,homodimeric probe molecules significantly optimized the imaging performance compared with monomeric probe molecules,including making the background signal lower,improving the fluorescence signal-to-noise ratio to protein,enhancing the protein affinity and kinetic binding process rate,and making the probe anti-interference ability improved.In this study,cytotoxicity experiments and in vitro protein fluorescence imaging experiments were performed to initially evaluate the ability of homodimer molecules to target Aβ proteins,and the results both demonstrated the feasibility of this molecular strategy.In addition,we investigated the effect of alkyl chain length on the homodimer probe molecule and further improved the strategy in order to screen for a better performing probe molecule.Taken together,the homodimer strategy can compensate for the shortcomings of probes to a certain extent and provide new ideas and solutions for probe synthesis and design strategies.