In-situ analytical methods are essential for the reliable observation of peptide reactions without perturbation of the system. In this work, a real-time in-situ NMR analysis was performed to gain insight into the initial stage of the aggregation of amyloid-beta (Aβ) 8–25 monomers, S8GY10EVHHQKLVFF20AEDVG25, in solution prior to the fibril formation. NMR chemical shift and intensity changes in combination with the CD spectra revealed no changes in Aβ secondary structure, but the presence of soluble, oligomeric intermediates followed by the appearance of insoluble and non-structured aggregates before β-fibril formation. Molecular views of intermediates and aggregation mechanisms were proposed in comparison with NMR spectral changes in wild-type Aβ 8–25 and its two mutants, A21G and E22G. The mutation of just one amino acid modified the aggregation properties of Aβ 8–25; it slowed or accelerated the fibril formation by controlling the progress of conversion from monomer to aggregate via a soluble, small oligomer.
M. T. Colvin, R. Silvers, Q. Z. Ni, T. V. Can, I. Sergeyev, M. Rosay, K. J. Donovan, B. Michael, J. Wall, S. Linse, R. G. Griffin. J. Am. Chem. Soc.138, 9663 (2016).10.1021/jacs.6b0512927355699)| false
S. I. A. Cohen, S. Linse, L. M. Luheshi, E. Hellstrand, D. A. White, L. Rajah, D. E. Otzen, M. Vendruscolo, C. M. Dobson, T. P. J. Knowles. Proc. Natl. Acad. Sci. U.S.A.110, 9758 (2013).2370391010.1073/pnas.1218402110)| false
C. Nilsberth, A. Westlind-Danielsson, C. B. Eckman, M. M. Condron, K. Axelman, C. Forsell, C. Stenh, J. Luthman, D. B. Teplow, S. G. Younkin, J. Näslund, L. Lannfelt. Nat. Neurosci.4, 887 (2001).10.1038/nn0901-88711528419)| false
S. A. Kozin, A. A. Kulikova, A. N. Israte, P. O. Tsvetkov, S. S. Zhokhov, Y. V. Mezentsev, O. I. Kechko, A. S. Ivanov, V. I. Polshakov, A. A. Makarov. Metallomics7, 422 (2015).2570316510.1039/C4MT00259H)| false
Pure and Applied Chemistry is the official monthly Journal of the International Union of Pure and Applied Chemistry (IUPAC), with responsibility for publishing works arising from those international scientific events and projects that are sponsored and undertaken by the Union.