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2021-03-25

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cc-by (c) Rol Rúa, Álvaro et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/188748

Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease

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Recurs relacionat

https://doi.org/10.1038/s41467-021-22076-5

Resum

Ulcerative colitis and Crohn's disease are forms of inflammatory bowel disease whose incidence and prevalence are increasing worldwide. These diseases lead to chronic inflammation of the gastrointestinal tract as a result of an abnormal response of the immune system. Recent studies positioned Cortistatin, which shows low stability in plasma, as a candidate for IBD treatment. Here, using NMR structural information, we design five Cortistatin analogs adopting selected native Cortistatin conformations in soln. One of them, A5, preserves the anti-inflammatory and immunomodulatory activities of Cortistatin in vitro and in mouse models of the disease. Addnl., A5 displays an increased half-life in serum and a unique receptor binding profile, thereby overcoming the limitations of the native Cortistatin as a therapeutic agent. This study provides an efficient approach to the rational design of Cortistatin analogs and opens up new possibilities for the treatment of patients that fail to respond to other therapies.

Matèries

Neuropèptids, Malalties inflamatòries intestinals, Malaltia de Crohn

Matèries (anglès)

Neuropeptides, Inflammatory bowel diseases, Crohn's disease

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Articles publicats en revistes (Química Inorgànica i Orgànica)

Citació

ROL RÚA, Álvaro, TODOROVSKI, Toni, MARTIN-MALPARTIDA, Pau, ESCOLÀ JANÉ, Anna, GONZÁLEZ-REY, Elena, ARAGÓN ALTARRIBA, Eric, VERDAGUER I ESPAULELLA, Xavier, VALLÈS MIRET, Mariona, FARRERA SINFREU, Josep maria, PUIG GOMÀ-CAMPS, Eduard, FERNÁNDEZ-CARNEADO, Jimena, PONSATI, Berta, DELGADO, Mario, RIERA I ESCALÉ, Antoni, MACÍAS HERNÁNDEZ, María j.. Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease. _Nature Communications_. 2021. Vol. 12, núm. 1869. [consulta: 20 de desembre de 2025]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/188748]

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