{"id":4143,"date":"2021-07-06T12:25:36","date_gmt":"2021-07-06T11:25:36","guid":{"rendered":"https:\/\/ibb.uab.cat\/?p=4143"},"modified":"2021-07-06T12:34:40","modified_gmt":"2021-07-06T11:34:40","slug":"nanomolar-affinity","status":"publish","type":"post","link":"https:\/\/ibb.uab.cat\/index.php\/2021\/07\/06\/nanomolar-affinity\/","title":{"rendered":"Protein Folding and Conformational Diseases: &#8220;\u03b1-Helical peptidic scaffolds to target \u03b1-synuclein toxic species with nanomolar affinity&#8221;"},"content":{"rendered":"\n<p><a href=\"https:\/\/www.nature.com\/ncomms\"><em>Nature Communications<\/em><\/a> <strong>volume&nbsp;12<\/strong>, Article&nbsp;number:&nbsp;3752 (2021)<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"alignleft size-large is-resized\"><img loading=\"lazy\" src=\"https:\/\/ibb.uab.cat\/wp-content\/uploads\/LL-37_G0.jpg\" alt=\"\" class=\"wp-image-4134\" width=\"384\" height=\"216\" srcset=\"https:\/\/ibb.uab.cat\/wp-content\/uploads\/LL-37_G0.jpg 480w, https:\/\/ibb.uab.cat\/wp-content\/uploads\/LL-37_G0-300x169.jpg 300w, https:\/\/ibb.uab.cat\/wp-content\/uploads\/LL-37_G0-462x260.jpg 462w\" sizes=\"(max-width: 384px) 100vw, 384px\" \/><\/figure><\/div>\n\n\n\n<h2 id=\"Abs1\">Abstract<\/h2>\n\n\n\n<p>\u03b1-Synuclein aggregation is a key driver of neurodegeneration in Parkinson\u2019s disease and related syndromes. Accordingly, obtaining a molecule that targets \u03b1-synuclein toxic assemblies with high affinity is a long-pursued objective. Here, we exploit the biophysical properties of toxic oligomers and amyloid fibrils to identify a family of \u03b1-helical peptides that bind to these \u03b1-synuclein species with low nanomolar affinity, without interfering with the monomeric functional protein. This activity is translated into a high anti-aggregation potency and the ability to abrogate oligomer-induced cell damage. Using a structure-guided search we identify a human peptide expressed in the brain and the gastrointestinal tract with analogous binding, anti-aggregation, and detoxifying properties. The chemical entities we describe here may represent a therapeutic avenue for the synucleinopathies and are promising tools to assist diagnosis by discriminating between native and toxic \u03b1-synuclein species.<\/p>\n\n\n\n<p><a href=\"https:\/\/www.nature.com\/articles\/s41467-021-24039-2\">https:\/\/www.nature.com\/articles\/s41467-021-24039-2<\/a><\/p>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Nature Communications volume&nbsp;12, Article&nbsp;number:&nbsp;3752 (2021) Abstract \u03b1-Synuclein aggregation is a key driver of neurodegeneration in Parkinson\u2019s disease and related syndromes. Accordingly, obtaining a molecule that targets \u03b1-synuclein toxic assemblies with high affinity is a long-pursued objective. Here, we exploit the biophysical properties of toxic oligomers and amyloid fibrils to identify a family of \u03b1-helical peptides [&hellip;]<\/p>\n","protected":false},"author":65,"featured_media":2489,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[4],"tags":[],"_links":{"self":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/4143"}],"collection":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/comments?post=4143"}],"version-history":[{"count":7,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/4143\/revisions"}],"predecessor-version":[{"id":4156,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/4143\/revisions\/4156"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media\/2489"}],"wp:attachment":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media?parent=4143"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/categories?post=4143"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/tags?post=4143"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}