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Comparisons of the NACP Self-Oligomerizations Induced by Aβ25-35 in the Presence of Dicyclohexylcarbodiimide and N-(Ethoxycarbonyl)-2-Ethoxy-1,2-Dihydroquinoline

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Abstract

NACP, the precursor protein of the non-amyloid β/A4 protein (Aβ) component of Alzheimer's disease (AD) amyloid, also known as α-synuclein was shown to undergo self-oligomerization only in the presence of a modified Aβ fragment (residues 25–35) by using a relatively hydrophobic coupling reagent, dicyclohexylcarbodiimide (DCCD). Since the oligomerization not only required a relatively high concentration of DCCD but also its efficiency was suppressed even at a slightly basic pH of 7.5, another coupling reagent called N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline (EEDQ) was examined in order to make use of this technique to access the functional aspects of NACP in vitro by exploring more accurate and reproducible reaction conditions. The EEDQ also gave rise to the NACP oligomerization only in the presence of Aβ25-35 among the variously modified Aβ peptides. The reagent was about three times more effective than DCCD in terms of its optimal concentration to visualize the oligomers. In addition, its oligomerizing potency was not affected by the basic condition. Although physiological and pathological significance of the NACP self-oligomerization are currently unknown, this dramatic phenomenon and its visualization technique could shed light on the determination of molecular relationships of NACP with various intracellular or extracellular biomolecules related to the pathological conditions of Alzheimer's and Parkinson's diseases.

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Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, Inha University, Nam-Ku, Inchon, 402-751, Korea

    Ju-Hyun Lee, Hyun-Ju Shin, Chung-Soon Chang & Seung R. Paik

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  1. Ju-Hyun Lee
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Lee, JH., Shin, HJ., Chang, CS. et al. Comparisons of the NACP Self-Oligomerizations Induced by Aβ25-35 in the Presence of Dicyclohexylcarbodiimide and N-(Ethoxycarbonyl)-2-Ethoxy-1,2-Dihydroquinoline. Neurochem Res 23, 1427–1434 (1998). https://doi.org/10.1023/A:1020711025418

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