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Activation of the Wnt Pathway by Small Peptides: Rational Design, Synthesis and Biological Evaluation
Author(s) -
Brogi Simone,
Maramai Samuele,
Brindisi Margherita,
Chemi Giulia,
Porcari Valentina,
Corallo Claudio,
Gennari Luigi,
Novellino Ettore,
Ramunno Anna,
Butini Stefania,
Campiani Giuseppe,
Gemma Sandra
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700551
Subject(s) - wnt signaling pathway , lrp6 , cytotoxicity , dkk1 , rational design , chemistry , lrp5 , osteoporosis , microbiology and biotechnology , biochemistry , receptor , computational biology , cancer research , biology , signal transduction , in vitro , endocrinology , genetics
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.