The Synthesis Of Multi-functional Peptide-polymer For Anti-alzheimer's Disease And Its Performance Study

Alzheimer's disease is a most typical neurodegenerative disease.In recent years,one of the biggest challenge on treatment of Alzheimer's disease is to keep the balance of beta amyloid(A?)in brain.Nanomaterials were widely used in many disease areas because of its unique property,including neurological diseases,which has great bioapplication value.Peptide-polymer,as a novel functional materials,have great excellent biological compatibility and safety.What's more,it can possess more than one biological effect by modifying different peptide residues on the polymer,which could improve the therapeutic effect.The nanomaterials not only increased the activity against Alzheimer's disease,but also made an effective evaluation on the treatment of Alzheimer's disease,which are significant for the research.Herein,we firstly synthesized the acrylic-chitosan(Acryl-CS)and peptide residues CFFVLKG-PEG368,which has multiple hydrogen bonds between the molecules.And we characterized them by nuclear magnetic resonance(NMR)and flight mass spectrum,respectively.Then the CFFVLKG-PEG368 and autophagy activation peptide(Beclin-1,CTNVFNATFHIWHSGQFGT,CFFVLKG-PEG368/ Beclin-1=1/1)was reacted with Acryl-CS by Michael addition reaction to obtain the system of peptide-polymer CS-K-B(M3),and the structure were studied by NMR.The M3 could self-assembled into nanoparticles with a diameter 43.8±11.1 nm in phosphate buffer saline,which were performed by transmission electron microscope.On the one hand,M3 nanomaterials contained peptide residues KLVFF comes from homologous sequence of A?,which could inhibit the fibrillation of A? by recognizing and co-assembling with A?.On the hand,the Beclin-1 was modified into M3,which could activate the autophagy of cell.So,when the co-assembly of M3 and A? entered into cell,they could degrade by autophagic degradation activated or up-regulated by Beclin-1 in M3.Therefore,the two methods reduced synergistically the neurotoxicity of A?,which were more effective for the therapy of Alzheimer's disease.