Structure-based design of a Cortistatin analog with improved immunoregulatory activity against inflammatory bowel disease (IBD)

Álvaro Rol, Toni Todorovski, Pau Martin-Malpartida, Anna Escolà, Elena Gonzalez-Rey, Eric Aragón, Xavier Verdaguer, Mariona Vallès-Miret, Josep Farrera-Sinfreu, Eduard Puig, Jimena Fernández-Carneado, Berta Ponsati, Mario Delgado, Antoni Riera, Maria J. Macias

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Received Date: 21st November 19

Ulcerative colitis and Crohn’s disease are inflammatory bowel diseases (IBD) that lead to chronic inflammations of the gastrointestinal tract due to an abnormal response of the immune system. Finding new effective drugs to tackle IBD represents a major therapeutic concern since IBD incidence and prevalence is increasing worldwide. Recent studies positioned Cortistatin (CST) as a candidate for IBD treatment due to its anti-inflammatory and immunomodulatory activity. Here, we studied the structural properties of CST using NMR and synthesized and characterized new analogs displaying enriched populations of some native conformations. One of them, Analog 5, preserved the activity against IBD with an increased half-life in serum, overcoming the native hormone limitation and opening the door for the use of CST analogs as therapeutic agents. This work represents a new approach to the rational design of molecules to treat IBD and a possibility for patients that fail to respond to other therapies.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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