Screenning The Peptide Against The Aggregation Of β-Amyloid Peptide Via Phage Display

Background:Because of the increased life expectancy and the decreased birth rate year by year,the aged population is growing quickly.High prevalence of dementia in the aged population has become a serious social problem.Alzheimer's disease(AD) is the lead cause for dementia in the elderly.Currently,however,few drugs have been approved for clinical treatment of the AD,i.e.,acetylcholinesterase inhibitors(e.g., donepezil) and N-methyl-D-aspartate receptor antagonist(e.g.,salt memantine).But these drugs can not reverse the pathologic changes of AD brain.Up to date,the treatment of AD is still in symptomatic level.At the present,the hypothesis accepted by researchers more and more is that increased Aβload is the initiating factor of AD onset and responsible for AD pathologic process.Therefore,the materials which against Aβassembly to form oligomers,and the senile plaques may eventually become the drugs of AD treatment reversed AD pathology.Objective:To screen a/some oligopeptide(s) which can specifically bind Aβ_1-10, and investigate whether the specific phages displaying the oligopeptide(s) can bind Aβand inhibite its aggregation.Methods:Aβ_1-10 which includes the EFRH,a sequence involved in Aβaggregation, was used to target molecular,and synthesized and labeled by biotin.A randomized 12-mer peptide library presented on M13 phages was used to screen the peptides (phages).Specificity of the selected phages to bind the bio-Aβ_1-10 was examined by BIAcore3000 instrument.The specific phages inhibite Aβaggregation in vitro was observed by transmission electron microscope.The oligopeptide(s) sequences displayed on the specific phages were also detected.Results:The phages which could bind to the Aβ_1-10 were acquired after 3 rounds of panning.The specificity of selected phages binding to Aβ_1-10 was identified.The specific phage could obviously inhibited Aβaggregation in vitro.Conclusion:These results suggested that the phages displaying specific oligopeptide(s) could have been acquired and prohibit Aβaggregation.