A green fluorescent protein chromophore analogue to promote self-assembly of diphenylalanine into fluorescent microtubes

Abstract It is known that misfolding and aggregation of amyloid-beta (Aβ) peptide was thought to be the causing of Alzheimer's disease (AD). Until now, there are no effective drugs for this disease. Therefore, it is necessary to develop excellent probes for early diagnosis and assisting drug research and development of AD. Diphenylalanine peptide (FF), as a key and the smallest core recognition sequence of amyloid-beta (Aβ) peptide, has attracted much attention. In this paper, we designed and synthesized meta- and para-amino green fluorescent protein chromophore analogues m-DBI and p-DBI. Comparing their fluorescence properties, we found that m-DBI displayed relatively strong fluorescence in aprotic organic solvents due to a large barrier for the Z→E photoisomerization, while it showed weak fluorescence in protic solvents as a result of solvent-solute H-bonding interactions. Importantly, it could drive and assemble with FF into microtubes with “turn-on” fluorescence. In contrast, p-DBI exhibited very weak fluorescence in both protic and aprotic solvents, which is due to the ultrafast Z→E photoisomerization. Furthermore, it could not co-assemble with FF and even displayed weak fluorescence in solid state. In addition, FF-m-DBI co-assembly microtubes could be partially disassembled through incubating with a potent inhibitor of Aβ aggregation EGCG, accompanied by a decrease in fluorescence intensity, shows the potential application of screening possible inhibitor molecules of AD diseases.