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Title: Activation of the Wnt pathway by small peptides: rational design, synthesis and biological evaluation
Authors: Brogi, Simone
Maramai, Samuele 
Brindisi, Margherita 
Chemi, Giulia 
Porcari, Valentina
Corallo, Claudio
Gennari, Luigi
Novellino, Ettore
Ramunno, Anna
Butini, Stefania 
Campiani, Giuseppe 
Gemma, Sandra 
Issue Date: 2017
Project: None 
A computational analysis of the X-ray structure of the low-density lipoprotein receptor-related protein 6 (LRP6) with the Dickkopf-1 (DKK1) C-terminal fragment has allowed us to rationally design a small set of decapeptides. These compounds behave as agonists of the canonical Wnt pathway in the micromolar range when tested on a dual luciferase Wnt functional assay in glioblastoma cells. Two of the oligopeptides showed a lack of cytotoxicity in human primary osteoblasts isolated from sponge bone tissue (femoral heads or knees of elderly patients). According to the mechanism of action, the studies revealed a dose- and time-dependent increase in the viability of human osteoblasts. These results may indicate a potential therapeutic application of this class of compounds in the treatment of bone diseases related to aging, such as osteoporosis.
ISSN: 1860-7179
DOI: 10.1002/cmdc.201700551
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