{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:51:41Z","timestamp":1793321501249,"version":"4.5.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,1,8]]},"abstract":"<jats:p>The self-assembly of abnormally folded proteins into amyloid fibrils is a hallmark of many debilitating diseases, from Alzheimer\u2019s and Parkinson diseases to prion-related disorders and diabetes type II. However, the fundamental mechanism of amyloid aggregation remains poorly understood. Core sequences of four to seven amino acids within natural amyloid proteins that form toxic fibrils have been used to study amyloidogenesis. We recently reported a class of systematically designed ultrasmall peptides that self-assemble in water into cross-\u03b2\u2013type fibers. Here we compare the self-assembly of these peptides with natural core sequences. These include core segments from Alzheimer\u2019s amyloid-\u03b2, human amylin, and calcitonin. We analyzed the self-assembly process using circular dichroism, electron microscopy, X-ray diffraction, rheology, and molecular dynamics simulations. We found that the designed aliphatic peptides exhibited a similar self-assembly mechanism to several natural sequences, with formation of \u03b1-helical intermediates being a common feature. Interestingly, the self-assembly of a second core sequence from amyloid-\u03b2, containing the diphenylalanine motif, was distinctly different from all other examined sequences. The diphenylalanine-containing sequence formed \u03b2-sheet aggregates without going through the \u03b1-helical intermediate step, giving a unique fiber-diffraction pattern and simulation structure. Based on these results, we propose a simplified aliphatic model system to study amyloidosis. Our results provide vital insight into the nature of early intermediates formed and suggest that aromatic interactions are not as important in amyloid formation as previously postulated. This information is necessary for developing therapeutic drugs that inhibit and control amyloid formation.<\/jats:p>","DOI":"10.1073\/pnas.1217742110","type":"journal-article","created":{"date-parts":[[2012,12,24]],"date-time":"2012-12-24T23:14:38Z","timestamp":1356390878000},"page":"519-524","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":130,"title":["Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis"],"prefix":"10.1073","volume":"110","author":[{"given":"Anupama","family":"Lakshmanan","sequence":"first","affiliation":[{"name":"Institute of Bioengineering and Nanotechnology, Singapore 138669;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Cheong","sequence":"additional","affiliation":[{"name":"Institute of High Performance Computing, Singapore 138632;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Accardo","sequence":"additional","affiliation":[{"name":"Istituto Italiano di Tecnologia, 16163 Genoa, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo","family":"Di Fabrizio","sequence":"additional","affiliation":[{"name":"Istituto Italiano di Tecnologia, 16163 Genoa, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Riekel","sequence":"additional","affiliation":[{"name":"European Synchrotron Radiation Facility, 38043 Grenoble Cedex 09, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte A. 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