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Synthetic availability of an A\u03b2 variant is often the key to study its role under physiological or pathological conditions. Herein, we report a protocol for the efficient solid\u2010phase peptide synthesis of the N\u2010terminally elongated A\u03b2\u2010peptides A\u03b2<jats:sub>\u22123\u201338<\/jats:sub>, A\u03b2<jats:sub>\u22123\u201340<\/jats:sub>, and A\u03b2<jats:sub>\u22123\u201342<\/jats:sub>. Biophysical characterization by NMR spectroscopy, CD spectroscopy, an aggregation assay, and electron microscopy revealed that all three peptides were prone to aggregation into amyloid fibrils. Immunoprecipitation, followed by mass spectrometry, indicated that A\u03b2<jats:sub>\u22123\u201338<\/jats:sub> and A\u03b2<jats:sub>\u22123\u201340<\/jats:sub> are generated by transfected cells even in the presence of a tripartite \u03b2\u2010site amyloid precursor protein cleaving enzyme\u20051 (BACE1) inhibitor. The elongated A\u03b2 peptides starting at Val(\u22123) can be separated from N\u2010terminally\u2010truncated A\u03b2 forms by high\u2010resolution isoelectric\u2010focusing techniques, despite virtually identical isoelectric points. The synthetic A\u03b2 variants and the methods presented here are providing tools to advance our understanding of the potential roles of N\u2010terminally elongated A\u03b2 variants in Alzheimer's disease.<\/jats:p>","DOI":"10.1002\/chem.201600892","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T01:49:12Z","timestamp":1462931352000},"page":"8685-8693","source":"Crossref","is-referenced-by-count":13,"title":["Solid\u2010Phase Synthesis and Characterization of N\u2010Terminally Elongated A\u03b2<sub>\u22123\u2013<i>x<\/i><\/sub>\u2010Peptides"],"prefix":"10.1002","volume":"22","author":[{"given":"Isaak","family":"Beyer","sequence":"first","affiliation":[{"name":"Department Chemie Technische Universit\u00e4t Dresden  Bergstrasse 66 01069 Dresden Germany"}]},{"given":"Nasrollah","family":"Rezaei\u2010Ghaleh","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biophysical Chemistry  Am Fassberg 11 37077 G\u00f6ttingen Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)  Von-Siebold-Str. 3a 37075 G\u00f6ttingen Germany"}]},{"given":"Hans\u2010Wolfgang","family":"Klafki","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Medical Center G\u00f6ttingen, Georg-August-Universit\u00e4t  37075 G\u00f6ttingen Germany"}]},{"given":"Olaf","family":"Jahn","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Experimental Medicine  Proteomics Group 37075 G\u00f6ttingen Germany"},{"name":"Center for Nanoscale Microscopy and Molecular Physiology of the Brain University Medical Center G\u00f6ttingen University of G\u00f6ttingen  Humboldtallee 23 37073 G\u00f6ttingen Germany"}]},{"given":"Ute","family":"Hau\u00dfmann","sequence":"additional","affiliation":[{"name":"University of Duisburg-Essen  45141 Essen Germany"}]},{"given":"Jens","family":"Wiltfang","sequence":"additional","affiliation":[{"name":"German Center for 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