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Abstract

In contrast to the general tendency of hydrophobicity-toxicity relationship of amyloid β peptide, we have previously found that the replacement of Asn27 of amyloid β(25–35) peptide with Ala yielded a more hydrophobic but less toxic analog and that of Met35 gave a less hydrophobic but more toxic one. To reveal the unique role of these two residues in the neurotoxicity of amyloid β(1–42) peptide, the major peptide constituent of amyloid plaques in human brain, we synthesized two analogs N27A and M35A in which Asn27 and Met35 of amyloid β(1–42) peptide was replaced with Ala, respectively. The former showed much weaker toxicity than the native peptide, while the latter showed almost an equivalent toxicity, indicating that the side chain amide group of Asn27 has an essential role for the toxicity of amyloid β peptides.

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Abbreviations

Aβ:

Amyloid β peptide

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

Boc:

t-Butoxycarbonyl

Fmoc:

9-Fluorenylmethoxycarbonyl

MALDI-TOF-MS:

Matrix assisted laser desorption/ionization time-of-flight mass spectrometry

MTT:

3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

ODS:

Octadecylsilane

TFA:

Trifluoroacetic acid

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Acknowledgments

This work was supported in part by a project grant from the Program for Promotion of Fundamental Studies in Health Sciences of Organization for Drug ADR Relief, R&D Promotion and Product Review of Japan. We thank Drs. Akihiko Takashima, Masami Takahashi, and Toshiyuki Kohno (Mitsubishi Kagaku Institute of Life Sciences) for helpful discussion.

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Correspondence to Kazuki Sato.

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Analogs are designated by a letter and number indicating the identity and position of the replaced amino acid, followed by a letter indicating the identity of the replacement; for example, N27A indicates an analog in which Asn27 is replaced with Ala.

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Sato, K., Maeda, T. & Hoshi, M. Asn27 is Essential for the Neurotoxicity of Amyloid β(1–42) Peptide. Int J Pept Res Ther 18, 341–345 (2012). https://doi.org/10.1007/s10989-012-9310-3

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  • DOI: https://doi.org/10.1007/s10989-012-9310-3

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