New Applications Of Quinalidine Red And Resazurin In Amyloid

The accumulation of amyloid fibrils in the body can cause a variety of diseases,such as Alzheimer's disease,type 2 diabetes,and Parkinson's disease.Therefore,protein amyloidosis research is an important topic at the intersection of chemistry,biology and medicine.To monitor the process of fibrillation and understand the mechanism of amyloid fiber formation,probes to detect protein entanglement and amyloid plaques are essential.Hunting for novel amyloid probes is critical as each new probe might provide distinct insight into amyloid science from a fresh angle.In this report,we describe a near-infrared fluorescent probe called quinaldine red(QR)which lights up the ?-sheet structure of amyloid fibrils.The photochemical and biophysical properties of QR along with other canonical amyloid probes in the presence of protein fibrils were investigated by using fluorescence spectroscopy,confocal fluorescent microscopy and isothermal titration calorimetry.Moreover,the binding sites and interaction mode between QR and insulin fibrils were calculated based on molecule docking.Among these amyloid probes,QR showed several advantages including strong supramolecular force,near-infrared emission,high sensitivity and resistance to bleaching.A linear response of the fluorescence intensity of QR towards fibril samples in the presence of sera was visualized in the range of 1–30 ?M,with the limit of detection of 2.31 ?M.The recovery and relative standard deviation of the proposed method for the determination of protein fibrils was 90.4%–99.2% and 3.05%–3.47%,respectively.Importantly,QR shows low biological background and high sensitivity in the detection of amyloid plaques in brain slices of pathogenic rats.We recommend QR as a novel and excellent alternative tool for monitoring conformational transition of amyloid proteins.In addition to the probes used to detect amyloid,in clinical applications,effective amyloid inhibitors are also crucial for the treatment of diseases.Currently there are few effective methods for treating amyloid diseases,so screening for new inhibitors of amyloid fibrosis is also an important task and a huge challenge.In this report,we experimentally found that resazurin can be used as an inhibitor ofinsulin fibrosis.The more prominent feature of this inhibitor is that even low content resazurin can achieve excellent inhibitory effects.In addition,the effect of this biocompatible dye on insulin is not limited to the nucleation stage of insulin fibrosis,and this inhibitory effect can be achieved at almost any stage in the fibrosis process.However,resorufin,the reduced product of resazurin,did not show this effect.Therefore,our findings can be used to develop amyloid inhibitors,and the redox couple can become a new platform and model for studying protein fibrosis.