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However, there is still a level of analysis that is only possible through wet laboratory experiments, especially in respect to the investigation of the pathological effect of mutations and posttranslational modifications (PTMs) on proteins of interest. This requires the availability of pure peptides and proteins in sufficient quantities for biophysical, biochemical, and functional studies. In this context, chemical protein synthesis and semi\u2010synthesis are powerful tools in protein research, which help to enlighten the role of protein modification in the physiology and pathology of proteins. A protein of high interest in the field of biomedicine is alpha\u2010synuclein (aSyn), a protein deeply associated with several devastating neurodegenerative disorders such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), or multiple systems atrophy (MSA). Here, we describe several methods and pathways to synthesize native or modified aSyn, and discuss how these approaches enable us to address pathological mechanisms that may open novel perspectives for therapeutic intervention.<\/jats:p>","DOI":"10.1002\/cbic.202400253","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T03:10:13Z","timestamp":1720149013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis and Semi\u2010Synthesis of Alpha\u2010Synuclein: Insight into the Chemical Complexity of Synucleinopathies"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-9361","authenticated-orcid":false,"given":"Luisa Maria","family":"Gatzemeier","sequence":"first","affiliation":[{"name":"Institute of Organic and Biomolecular Chemistry University of G\u00f6ttingen  Tammannstra\u00dfe 2 37077 G\u00f6ttingen Germany"},{"name":"Department of Experimental Neurodegeneration Center for Biostructural Imaging of Neurodegeneration University Medical Center G\u00f6ttingen  Waldweg 33 37073 G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8613-7862","authenticated-orcid":false,"given":"Franc","family":"Meyer","sequence":"additional","affiliation":[{"name":"Institute of Inorganic Chemistry University of G\u00f6ttingen  Tammannstra\u00dfe 4 37077 G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1679-1727","authenticated-orcid":false,"given":"Tiago Fleming","family":"Outeiro","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration Center for Biostructural Imaging of Neurodegeneration University Medical Center G\u00f6ttingen  Waldweg 33 37073 G\u00f6ttingen Germany"},{"name":"Max Planck Institute for Multidisciplinary Sciences  Hermann-Rein-Stra\u00dfe 3 37075 G\u00f6ttingen Germany"},{"name":"Translational and Clinical Research Institute Faculty of Medical Sciences Newcastle University  Framlington Place Newcastle Upon Tyne NE2 4HH United Kingdom"},{"name":"Scientific employee with an honorary contract at Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE)  Von Siebold-Stra\u00dfe 3a 37075 G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13249"},{"key":"e_1_2_8_2_1","unstructured":"\u00a0"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pbr.2019.10.005"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020375"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2016.06.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000671"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-150642"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12125"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.318949"},{"key":"e_1_2_8_10_1","unstructured":"\u00a0"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000112832"},{"key":"e_1_2_8_12_2","doi-asserted-by":"crossref","unstructured":"C. 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