The Impact Of Patent Blue V Calcium And Victoria Blue B Toward Amyloid Fibrilization

Amyloid-insoluble fibrils are formed by opening the folded normal proteins under certain conditions and exposing the hydrophobic surface to facilitate the continuous aggregation of soluble monomers to form insoluble fibrils,and the abnormal accumulation of such proteins in human organs or cells can cause many neurological diseases,such as alzheimer's disease,huntington's disease,type ii diabetes,parkinson's and so on.Therefore,in recent years,many laboratories have begun to study the identification and inhibition of amyloid probes.Firstly,for the recognition probe,many kinds of materials have been invented.among them,the dye is a classical fluorescent probe.The most classic discovered sulforaphane T,curcumin and so on are widely used as well as market-oriented,because of their broad-spectrum and high sensitivity,almost all amyloid can be monitored.However,the thioflavin T and so on has low anti-jamming ion property,and it emits green fluorescence,which interferes with the background of the sample.In this study,after extensive screening work,it was found that a market dye,Victoria Blue B(VBB),could recognize the fibrils modeled of lysozyme protein,which could not emit light or faint fluorescence in aqueous solution and lysozyme protein.But with more and more hydrophobic surface exposure,the ability of VBB to combine with it becomes more and more strong,and the red fluorescence of emission at 680 nm is gradually strong.Compared with the classical dyes,VBB has the advantages of good anti-interference,low background and normal working in real samples such as serum.We have also confirmed by two similar derivatives of VBB that the luminescent group is a phenyl group linked to the amino group acting as a switching action.In term of inhibitors,the identification probe can find out the problem,but theinhibitor is the key to solve the problem,it is still a hot topic to develop the inhibitor to realize the clinical application.In order to achieve the dual-probe action and achieve lower inhibition concentration and targeting in human body,we designed a protein(bovine serum albumin(BSA))-based nano materials VBB-FPNs,firstly,using the fluorescence spectrum to confirm the fluorescence intensity of adding VBB-FPNs under the condition of lysozyme fibrosis remain unchange.Again,it was confirmed that VBB-FPNs could protect the ?-helix structure of lysozyme proprotein,but also confirmed by atomic force,transmission electron microscope and so on that the morphology of the protein was almost unchanged after adding VBB-FPNs.Therefore,VBB-FPNs is a potential amyloid inhibitor.We later found another amyloid protein modeled-bovine insulin,using Th T fluorescence method to prove that another dye PBV has inhibitory effect on bovine insulin formation fibrils.Through molecular docking,we also confirmed that strong binding of PBV to bovine insulin proprotein by hydrogen bonding and electrostatic action,so that the ultralow inhibition concentration can achieve good inhibition effect,which is 10-100 times lower than that of other small inhibitors.it is a very good small molecule inhibitor with low toxicity above 2 times higher than the working concentration,and it is expected to achieve low dose medicinal value.