Portal de Periódicos da CAPES

Enhancement of the inhibitory effect of an IL‐15 antagonist peptide by alanine scanning

2011; Wiley; Volume: 18; Issue: 1 Linguagem: Inglês

10.1002/psc.1411

1099-1387

Alicia Santos Savio, Osvaldo Reyes Acosta, Haydee Gerónimo Pérez, Yunier Rodríguez Álvarez, Araceli Chico, Hilda Garay Pérez, Miriam Ojeda Ojeda, Celia Aurora Arrieta Aguero, Miguel Estévez, Gerardo Guillén Nieto,

Herpesvirus Infections and Treatments

IL‐15 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‐15 antagonist peptide corresponding to sequence 36–45 of IL‐15 (KVTAMKCFLL) named P8, which specifically binds to IL‐15R α and inhibits IL‐15 biological activity with a half maximal inhibitory concentration (IC50) of 130 µ m in CTLL‐2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL‐15R α , 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‐15R α . We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non‐charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24 µ m . We also found that this peptide was more active than peptide P8 in the inhibition of TNF α secretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL‐15 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.