A robust preparation method for the amyloidogenic and intrinsically disordered amyloid-α peptide.

A robust preparation method for the amyloidogenic and intrinsically disordered amyloid-α peptide.
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DOI:
10.1002/psc.3414
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发表时间:
2022-10
影响因子:
2.1
通讯作者:
Raskatov, Jevgenij A.
Raskatov, Jevgenij A.
中科院分区:
生物学4区
文献类型:
--
作者:
Kuhn, Ariel J.;Raskatov, Jevgenij A.

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Recent findings suggest that amyloid-β may not the only peptidic culprit for the cognitive decline observed in patients with Alzheimer’s disease. A C-terminal fragment of Aβ, amyloid-α (Aα), also known as p3, has been shown to form amyloidogenic oligomers and fibrils more rapidly than Aβ. However, the insolubility and aggregation propensity of this 24–26-residue peptide makes it exceptionally difficult to produce, purify, and subsequently study. This paper reports a reproducible, multi-step method for the purification and pre-treatment of Aα and related analogues, yielding 95–99% pure peptides. We anticipate that the methods described herein will permit previously inaccessible biophysical and biological experiments that may be critical to understanding the role of this too long overlooked peptide in AD disease pathology. Obtaining pure amyloid-α (Aα) in its unaggregated form is a major challenge in Alzheimers’s disease research. A reproducible, multi-step method for the purification and pre-treatment of Aα and related analogues is reported, yielding 95–99% pure peptides. Reverse-phase PLRP-S columns are employed under basic conditions, in conjunction with filtration and careful storage techniques.
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