{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:59:12Z","timestamp":1768870752493,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,11,3]],"date-time":"2011-11-03T00:00:00Z","timestamp":1320278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Peptide Science"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:p>IL\u201015 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL\u201015 antagonist peptide corresponding to sequence 36\u201345 of IL\u201015 (KVTAMKCFLL) named P8, which specifically binds to IL\u201015R<jats:italic>\u03b1<\/jats:italic> and inhibits IL\u201015 biological activity with a half maximal inhibitory concentration (IC50) of 130\u2009\u00b5 <jats:sc>m<\/jats:sc> in CTLL\u20102 proliferation assay. In order to improve binding of peptide P8 to the receptor IL\u201015R<jats:italic>\u03b1<\/jats:italic>, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL\u201015R<jats:italic>\u03b1<\/jats:italic>. We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non\u2010charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24\u2009\u00b5<jats:sc>m<\/jats:sc>. We also found that this peptide was more active than peptide P8 in the inhibition of TNF<jats:italic>\u03b1<\/jats:italic> secretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL\u201015 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis. Copyright \u00a9 2011 European Peptide Society and John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/psc.1411","type":"journal-article","created":{"date-parts":[[2011,11,3]],"date-time":"2011-11-03T04:05:37Z","timestamp":1320293137000},"page":"25-29","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Enhancement of the inhibitory effect of an IL\u201015 antagonist peptide by alanine scanning"],"prefix":"10.1002","volume":"18","author":[{"given":"Alicia Santos","family":"Savio","sequence":"first","affiliation":[{"name":"Pharmaceutical Division Center for Genetic Engineering and Biotechnology  CP 10600 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osvaldo Reyes","family":"Acosta","sequence":"additional","affiliation":[{"name":"Chemistry and Physics Division Center for Genetic Engineering and Biotechnology  CP 10600 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haydee Ger\u00f3nimo","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Quality Control Division Center for Genetic Engineering and Biotechnology  CP 10600 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunier Rodr\u00edguez","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Quality Control Division Center for Genetic Engineering and Biotechnology  CP 10600 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Araceli","family":"Chico","sequence":"additional","affiliation":[{"name":"Rheumatology Department Hermanos Ameijeiras Hospital  San Lazaro 701 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilda Garay","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Chemistry and Physics Division Center for Genetic Engineering and Biotechnology  CP 10600 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam Ojeda","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Pharmaceutical Division Center for Genetic Engineering and Biotechnology  CP 10600 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia Aurora Arrieta","family":"Aguero","sequence":"additional","affiliation":[{"name":"Pharmaceutical Division Center for Genetic Engineering and Biotechnology  CP 10600 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Est\u00e9vez","sequence":"additional","affiliation":[{"name":"Rheumatology Department Hermanos Ameijeiras Hospital  San Lazaro 701 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo Guillen","family":"Nieto","sequence":"additional","affiliation":[{"name":"Pharmaceutical Division Center for Genetic Engineering and Biotechnology  CP 10600 Havana Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,11,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2003.10.005"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00035.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610036200"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403182200"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600240103"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0296-175"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.7.3608"},{"issue":"2","key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"910","DOI":"10.4049\/jimmunol.157.2.910","article-title":"Role of IL\u201015, IL\u20102 and their receptors in the development of T cell alveolitis in pulmonary sarcoidosis","volume":"157","author":"Agostini C","year":"1996","journal-title":"J. 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