ChemMedChem
ChemMedChem
5 years ago

Activation of the Wnt pathway by small peptides: rational design, synthesis and biological evaluation

Giuseppe Campiani, Samuele Maramai, Simone Brogi, Giulia Chemi, Stefania Butini, Claudio Corallo, Valentina Porcari, Luigi Gennari, Anna Ramunno, Sandra Gemma, Ettore Novellino, Margherita Brindisi
A computational analysis of the X-ray structure of the low-density lipoprotein receptor-related protein 6 (LRP6) with Dickkopf-1 (DKK1) C-terminal fragment has allowed us to rationally design a small set of decapeptides (1a-e). 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. Lack of cellular toxicity was assessed for compounds 1c and 1d in human primary osteoblasts isolated from sponge bone tissue (femoral heads or knee of old patients). According to the mechanism of action, the studies evidenced a dose- and time-dependent increase in the vitality 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/cmdc.201700551

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