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.

Activation of the Wnt Pathway by Small Peptides: Rational Design, Synthesis and Biological Evaluation.

Ramunno A;
2017-01-01

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/4708091
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