{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:38:55Z","timestamp":1777462735422,"version":"3.51.4"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (Portugal)","award":["PTDC\/NEU-NMC\/2138\/2014"],"award-info":[{"award-number":["PTDC\/NEU-NMC\/2138\/2014"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (Portugal)","award":["UID\/Multi\/04046\/2013"],"award-info":[{"award-number":["UID\/Multi\/04046\/2013"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (Portugal)","award":["SFRH\/BD\/114390\/2016"],"award-info":[{"award-number":["SFRH\/BD\/114390\/2016"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (Portugal)","award":["SFRH\/BD\/101171\/2014"],"award-info":[{"award-number":["SFRH\/BD\/101171\/2014"]}]},{"DOI":"10.13039\/501100005032","name":"Bial Foundation","doi-asserted-by":"publisher","award":["PT\/FB\/BL-2014-343"],"award-info":[{"award-number":["PT\/FB\/BL-2014-343"]}],"id":[{"id":"10.13039\/501100005032","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FEBS - Federation Biochemical Societies","award":["Summer Fellowship"],"award-info":[{"award-number":["Summer Fellowship"]}]},{"name":"COST Action TD1304 \u2013 the Network for the Biology of Zinc","award":["Zinc-Net - Training Internship"],"award-info":[{"award-number":["Zinc-Net - Training Internship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>S100 proteins assume a diversity of oligomeric states including large order self-assemblies, with an impact on protein structure and function. Previous work has uncovered that S100 proteins, including S100B, are prone to undergo \u03b2-aggregation under destabilizing conditions. This propensity is encoded in aggregation-prone regions (APR) mainly located in segments at the homodimer interface, and which are therefore mostly shielded from the solvent and from deleterious interactions, under native conditions. As in other systems, this characteristic may be used to develop peptides with pharmacological potential that selectively induce the aggregation of S100B through homotypic interactions with its APRs, resulting in functional inhibition through a loss of function. Here we report initial studies towards this goal. We applied the TANGO algorithm to identify specific APR segments in S100B helix IV and used this information to design and synthesize S100B-derived APR peptides. We then combined fluorescence spectroscopy, transmission electron microscopy, biolayer interferometry, and aggregation kinetics and determined that the synthetic peptides have strong aggregation propensity, interact with S100B, and may promote co-aggregation reactions. In this framework, we discuss the considerable potential of such APR-derived peptides to act pharmacologically over S100B in numerous physiological and pathological conditions, for instance as modifiers of the S100B interactome or as promoters of S100B inactivation by selective aggregation.<\/jats:p>","DOI":"10.3390\/molecules26020440","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T11:39:55Z","timestamp":1611056395000},"page":"440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting S100B with Peptides Encoding Intrinsic Aggregation-Prone Sequence Segments"],"prefix":"10.3390","volume":"26","author":[{"given":"Joana S.","family":"Crist\u00f3v\u00e3o","sequence":"first","affiliation":[{"name":"Biosystems and Integrative Sciences Institute, Faculdade de Ci\u00eancias, Universidade Lisboa, 1749-016 Lisbon, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade Lisboa, 1749-016 Lisbon, Portugal"}]},{"given":"Mariana A.","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"Biosystems and Integrative Sciences Institute, Faculdade de Ci\u00eancias, Universidade Lisboa, 1749-016 Lisbon, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade Lisboa, 1749-016 Lisbon, Portugal"}]},{"given":"Rodrigo","family":"Gallardo","sequence":"additional","affiliation":[{"name":"VIB Switch Laboratory, Flanders Institute for Biotechnology (VIB), 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, PB 802, 3000 Leuven, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-0168","authenticated-orcid":false,"given":"Joost","family":"Schymkowitz","sequence":"additional","affiliation":[{"name":"VIB Switch Laboratory, Flanders Institute for Biotechnology (VIB), 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, PB 802, 3000 Leuven, Belgium"}]},{"given":"Frederic","family":"Rousseau","sequence":"additional","affiliation":[{"name":"VIB Switch Laboratory, Flanders Institute for Biotechnology (VIB), 3000 Leuven, Belgium"},{"name":"Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, PB 802, 3000 Leuven, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4662-6933","authenticated-orcid":false,"given":"Cl\u00e1udio M.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Biosystems and Integrative Sciences Institute, Faculdade de Ci\u00eancias, Universidade Lisboa, 1749-016 Lisbon, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade Lisboa, 1749-016 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/156652413804486214","article-title":"Functions of S100 proteins","volume":"13","author":"Donato","year":"2013","journal-title":"Curr. 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