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.

Brogi, S., Maramai, S., Brindisi, M., Chemi, G., Porcari, V., Corallo, C., et al. (2017). Activation of the Wnt pathway by small peptides: rational design, synthesis and biological evaluation. CHEMMEDCHEM, 12(24), 2074-2085 [10.1002/cmdc.201700551].

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

Brogi, Simone;Maramai, Samuele;Brindisi, Margherita;Chemi, Giulia;Corallo, Claudio;Gennari, Luigi;RAMUNNO, ANNA;Butini, Stefania
;
Campiani, Giuseppe
;
Gemma, Sandra
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.
Brogi, S., Maramai, S., Brindisi, M., Chemi, G., Porcari, V., Corallo, C., et al. (2017). Activation of the Wnt pathway by small peptides: rational design, synthesis and biological evaluation. CHEMMEDCHEM, 12(24), 2074-2085 [10.1002/cmdc.201700551].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1023116