以表位模拟肽为亲和靶标的肉毒毒素受体结合抑制剂的筛选及鉴定

以设计合成的A型肉毒毒素表位模拟肽为亲和靶标,对噬菌体随机肽库进行筛选,寻找能与A型肉毒毒素表位模拟肽特异结合并能拮抗毒素毒性效应的分子,通过ELISA鉴定阳性克隆,并对鉴定的阳性克隆进行特异性分析及DNA测序。氨基酸序列同源性分析发现,针对P4、P5表位模拟肽获得了两条特异的结合序列,并通过动物保护实验在噬菌体展示肽水平对特异结合分子的毒素毒性拮抗效应进行了初步研究,初步证明结合肽对A型肉毒毒素有一定的保护作用。

Screening of Botulinum Neurotoxin type A-binding peptides by phage display peptide library

To seek effective inhibitor against BoNT/A,in this study,BoNT/A-binding peptides were screened from phage display peptide library using synthesized and identified mimicry peptides that contained antigenic epitopes as targets.According to the homology of the amino acid sequences of displayed peptides,most had same motifs respectively.ELISA assay confirmed that identified positive clones respectively against P4 and P5 could specifically bind BoNT/A.The mice assay showed the specific BoNT/A-binding peptides could partially protect against challenge of BoNT/A.The results from the study may aid in the future identification of more potent small molecule inhibitors against BoNT/A.