Activation of the Wnt Pathway by Small Peptides: Rational Design, Synthesis and Biological Evaluation.
ChemMedChem
; 12(24): 2074-2085, 2017 12 19.
Article
em En
| MEDLINE
| ID: mdl-29131552
ABSTRACT
A computational analysis of the X-ray structure of the low-density lipoprotein receptor-related proteinâ
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Osteoblastos
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Desenho de Fármacos
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Peptídeos e Proteínas de Sinalização Intercelular
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Bibliotecas de Moléculas Pequenas
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Via de Sinalização Wnt
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article