Yuan Dan, Shi Junfeng, Du Xuewen, Zhou Ning, Xu Bing
Department of Chemistry, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, United States.
J Am Chem Soc. 2015 Aug 19;137(32):10092-5. doi: 10.1021/jacs.5b05888. Epub 2015 Aug 5.
Despite the recent consensus that the oligomers of amyloid peptides or aberrant proteins are cytotoxic species, there is still a need for an effective way to eliminate the oligomers. Based on the fact that normal proteins are more glycosylated than pathogenic proteins, we show that a conjugate of nucleobase, peptide, and saccharide binds to peptides from molecular nanofibrils and accelerates the proteolytic degradation of the molecular nanofibrils. As the first example of the use of supramolecular glycosylation to dissociate molecular nanofibrils and to accelerate the degradation of peptide aggregates, this work illustrates a new method that ultimately may lead to an effective approach for degrading cytotoxic oligomers of peptides or aberrant proteins.
尽管最近已达成共识,即淀粉样肽或异常蛋白质的寡聚体是细胞毒性物质,但仍需要一种有效的方法来消除这些寡聚体。基于正常蛋白质比致病蛋白质具有更多糖基化的事实,我们表明,一种核碱基、肽和糖类的共轭物可与分子纳米纤维中的肽结合,并加速分子纳米纤维的蛋白水解降解。作为使用超分子糖基化来解离分子纳米纤维并加速肽聚集体降解的首个实例,这项工作阐明了一种新方法,该方法最终可能会带来一种有效降解肽或异常蛋白质的细胞毒性寡聚体的途径。