{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:07:05Z","timestamp":1769504825040,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,18]],"date-time":"2024-02-18T00:00:00Z","timestamp":1708214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PhD","award":["SFRH\/BD\/151016\/2021"],"award-info":[{"award-number":["SFRH\/BD\/151016\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Amyloidosis is a group of protein misfolding diseases, which include spongiform encephalopathies, Alzheimer\u2019s disease and transthyretin (TTR) amyloidosis; all of them are characterized by extracellular deposits of an insoluble fibrillar protein. TTR amyloidosis is a highly debilitating and life-threatening disease. Patients carry less stable TTR homotetramers that are prone to dissociation into non-native monomers, which in turn rapidly self-assemble into oligomers and, ultimately, amyloid fibrils. Liver transplantation to induce the production of wild-type TTR was the only therapeutic strategy until recently. A promising approach to ameliorate transthyretin (TTR) amyloidosis is based on the so-called TTR kinetic stabilizers. More than 1000 TTR stabilizers have already been tested by many research groups, but the diversity of experimental techniques and conditions used hampers an objective prioritization of the compounds. One of the most reliable and unambiguous techniques applied to determine the structures of the TTR\/drug complexes is X-ray diffraction. Most of the potential inhibitors bind in the TTR channel and the crystal structures reveal the atomic details of the interaction between the protein and the compound. Here we suggest that the stabilization effect is associated with a compaction of the quaternary structure of the protein and propose a scoring function to rank drugs based on X-ray crystallography data.<\/jats:p>","DOI":"10.3390\/molecules29040895","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T05:42:46Z","timestamp":1708494166000},"page":"895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibitors of Transthyretin Amyloidosis: How to Rank Drug Candidates Using X-ray Crystallography Data"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5063-515X","authenticated-orcid":false,"given":"Jos\u00e9 P.","family":"Leite","sequence":"first","affiliation":[{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6562-3730","authenticated-orcid":false,"given":"Diogo","family":"Costa-Rodrigues","sequence":"additional","affiliation":[{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8352-6539","authenticated-orcid":false,"given":"Lu\u00eds","family":"Gales","sequence":"additional","affiliation":[{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1021\/ar020073i","article-title":"Native state kinetic stabilization as a strategy to ameliorate protein misfolding diseases: A focus on the transthyretin amyloidoses","volume":"38","author":"Johnson","year":"2005","journal-title":"Acc. 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