Solvent effect on aggregational properties of b -amyloid polypeptides studied by FT–IR spectroscopy Z. Szabo ´ a , K. Jost a , K. Soo ´s a , M. Zara ´ndi a , J.T. Kiss b, * , B. Penke a a Department of Medical Chemistry, Albert Szent-Gyo ¨rgyi Medical University, Do ´m te ´r 8, H-6720 Szeged, Hungary b Department of Organic Chemistry, Attila Jo ´zsef University Do ´m te ´r 8, H-6720 Szeged, Hungary Received 24 August 1998; accepted 4 November 1998 Abstract Aggregation of the b -amyloid peptides is the major hallmark of the brain in case of Alzheimer’s disease. On the basis of some results it is assumed that the toxic centrum of the b A4 (1–42) amyloid peptide is primarily the (31–35) fragment [N.W. Kowall, A.C. McKee, B.A. Yanker, M.P. Beal, Neurobiol. Aging 13 537–542; B. Penke, L. To ´ th, K. Soo ´ s, J. Varga, E.Z. Szabo ´, J. Ma ´rki-Zay, A. Baranyi, in: H.L.S. Maia (Ed.), Peptides 1994, Proceedings of the 23rd European Peptide Symposium Escom, Leiden, 1995, pp. 101–102; I. Laczko ´ , Z. Ko ´ nya, J. Varga, K. Soo ´ s, M. Hollo ´ si, B. Penke, in: H.L.S. Maia (Ed.), Peptides 1994, Proceedings of the 23rd European Peptide Symposium Escom, Leiden, 1995, pp. 549–550]. Two analogues of b A4 (1–42) were synthetized: one of them includes the toxic fragment (31–35) unchanged and consists mainly of hydrophilic residues, denoted as MOD-3. The other one does not contain the toxic fragment and has mainly hydrophobic residues, denoted as MOD- 4. Peptides were dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol to have deaggregated samples. After the addition of the D 2 O as second solvent, the aggregation was followed by FT–IR spectroscopy. Changes of the spectra as a function of the composition of the solvent mixtures will be shown and discussed. Based on the results, FT–IR spectroscopy seems to be a suitable analytical control in standardizing the aggregation grade of b -amyloid peptides.  1999 Elsevier Science B.V. All rights reserved. Keywords: Alzheimer’s disease; b -amyloids; Aggregation; Solvent effect; 2D FT–IR 1. Introduction The amyloid precursor protein (APP) which is a neuroprotective membrane protein has a key role in Alzheimer’s disease [1–5]. It has several different molecular forms; among them APP695 is particularly abundant in neurons. In addition to the main routes, the cleavage of APP could take place on alternative pathways too, producing more or less water-soluble b -amyloid polypeptides. The abnormal accumulation of these latter sequences give possibilities to form b - conformation and b -turn containing structures which leads to aggregation and water insolubility. The ensuing formation of filaments and plaques followed by a serious neuronal cell loss is characterized as the Alzheimer’s disease [4–6]. Aggregation of the b -amyloids is strongly affected by concentration, pH, temperature etc. Study of the influence of the different parameters on the aggrega- tional properties of b -amyloids and their synthetic analogues can reveal essential data to the prevention of the undesirable transformations. Standardization of the aggregation grade of b -amyloid peptides is also essential for reproducible biological experiments. The aim of our work was to follow the aggregation of b A4 (1–42) peptide and its two synthetic Journal of Molecular Structure 480–481 (1999) 481–487 0022-2860/99/$ - see front matter  1999 Elsevier Science B.V. All rights reserved. PII: S0022-2860(98)00820-5 * Corresponding author.